JP2018509379A - Pesticide active heterocyclic derivatives with sulfur-containing substituents - Google Patents

Abstract

Compounds of formula (I) (wherein the substituents are as defined in claim 1) and agrochemically acceptable salts, stereoisomers, enantiomers, tautomers of these compounds The body and N-oxides can be used as insecticides and can be prepared in a manner known per se.

Description

  The present invention relates to pesticidally active, in particular pesticidal active heterocyclic derivatives containing sulfur substituents, intermediates for the preparation of these compounds, compositions comprising these compounds, and It relates to their use for controlling animal pests, including arthropods, in particular representatives of insects or Acarina.

  Heterocyclic compounds having pesticidal action are known and are described, for example, in WO 2012/0886848 and WO 2013/018928.

  Here, new pesticidally active heterocyclic 6 / 5-bicyclic ring derivatives having sulfur-containing phenyl and pyridyl substituents that are further substituted with cycloalkyl groups have been discovered.

（式中、
Ａが、ＣＨまたはＮを表し；
Ｑが、３位または４位に結合され；かつＣ₃〜Ｃ₆シクロアルキル、またはハロゲン、シアノ、Ｃ₁〜Ｃ₄アルキル、Ｃ₁〜Ｃ₄ハロアルキル、Ｃ₃〜Ｃ₆シクロアルキル、−Ｃ（Ｏ）ＯＨ、−Ｃ（Ｏ）ＮＨ₂、フェニルからなる群から選択される置換基で一置換または多置換されるＣ₃〜Ｃ₆シクロアルキル、およびハロゲン、シアノ、Ｃ₁〜Ｃ₄アルキル、Ｃ₁〜Ｃ₄ハロアルキル、Ｃ₁〜Ｃ₄ハロアルコキシ、Ｃ₁〜Ｃ₄アルコキシ、Ｃ₁〜Ｃ₄ハロアルキルスルファニル、Ｃ₁〜Ｃ₄ハロ−アルキルスルフィニル、Ｃ₁〜Ｃ₄ハロアルキルスルホニルおよび−Ｃ（Ｏ）Ｃ₁〜Ｃ₄ハロアルキルからなる群から選択される置換基で一置換または多置換され得るフェニルであり；
Ｘが、Ｓ、ＳＯまたはＳＯ₂であり；
Ｒ₁が、Ｃ₁〜Ｃ₄アルキル、Ｃ₁〜Ｃ₄ハロアルキル、Ｃ₃〜Ｃ₆シクロアルキル、Ｃ₃〜Ｃ₆シクロアルキル−Ｃ₁〜Ｃ₄アルキルまたはハロゲン、シアノおよびＣ₁〜Ｃ₄アルキルからなる群から選択される置換基で一置換または多置換されるＣ₃〜Ｃ₆シクロアルキルであり；または
Ｒ₁が、ハロゲン、シアノおよびＣ₁〜Ｃ₄アルキルからなる群から選択される置換基で一置換または多置換されるＣ₃〜Ｃ₆シクロアルキル−Ｃ₁〜Ｃ₄アルキルであり；または
Ｒ₁が、Ｃ₂〜Ｃ₆アルケニル、Ｃ₂〜Ｃ₆ハロアルケニルまたはＣ₂〜Ｃ₆アルキニルであり；
Ｒ₂が、ハロゲン、シアノ、Ｃ₁〜Ｃ₆ハロアルキルまたはヒドロキシル、メトキシおよびシアノからなる群から選択される１つまたは２つの置換基で置換されるＣ₁〜Ｃ₆ハロアルキルであり；または
Ｒ₂が、Ｃ₁〜Ｃ₄ハロアルキルスルファニル、Ｃ₁〜Ｃ₄ハロアルキルスルフィニル、Ｃ₁〜Ｃ₄ハロアルキルスルホニル、Ｏ（Ｃ₁〜Ｃ₄ハロアルキル）、または−Ｃ（Ｏ）Ｃ₁〜Ｃ₄ハロアルキルであり；または
Ｒ₂が、ハロゲン、シアノおよびＣ₁〜Ｃ₄アルキルからなる群から選択される置換基で一置換または多置換され得るＣ₃〜Ｃ₆シクロアルキルであり；
Ｘ₁が、Ｏ、ＳまたはＮＲ₃であり、ここで、Ｒ₃が、水素、Ｃ₁〜Ｃ₄アルキル、Ｃ₂〜Ｃ₆アルケニル、Ｃ₂〜Ｃ₆アルキニル、Ｃ₁〜Ｃ₄アルコキシ−Ｃ₁〜Ｃ₄アルキルまたはＣ₃〜Ｃ₆シクロアルキルである）
の化合物、ならびにそれらの化合物の農芸化学的に許容できる塩、立体異性体、鏡像異性体、互変異性体およびＮ−オキシドに関する。 Accordingly, the present invention provides compounds of formula I

(Where
A represents CH or N;
Q is 3 or 4 coupled to a position; and C ₃ -C ₆ cycloalkyl or halogen, cyano, C ₁ -C ₄ alkyl,, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ cycloalkyl, -C (O) OH, —C (O) NH ₂ , C ₃ -C ₆ cycloalkyl mono- or polysubstituted with a substituent selected from the group consisting of phenyl, and halogen, cyano, C ₁ -C ₄ alkyl , C ₁ -C ₄ haloalkyl, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkyl sulfinyl, C ₁ -C ₄ haloalkylsulfonyl and - Phenyl which may be mono- or polysubstituted with a substituent selected from the group consisting of C (O) C ₁ -C ₄ haloalkyl;
X is S, SO or SO ₂ ;
R ₁ is C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl-C ₁ -C ₄ alkyl or halogen, cyano and C ₁ -C ₄ C ₃ -C ₆ cycloalkyl which is mono- or polysubstituted with a substituent selected from the group consisting of alkyl; or R ₁ is selected from the group consisting of halogen, cyano and C ₁ -C ₄ alkyl C ₃ -C ₆ cycloalkyl-C ₁ -C ₄ alkyl mono- or polysubstituted by substituents; or R ₁ is C ₂ -C ₆ alkenyl, C ₂ -C ₆ haloalkenyl or C _2- C ₆ alkynyl;
R ₂ is halogen, cyano, C ₁ -C ₆ haloalkyl or hydroxy, C ₁ -C ₆ haloalkyl substituted with 1 or 2 substituents selected from the group consisting of methoxy and cyano; or R ₂ but it is C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkylsulfinyl, C ₁ -C ₄ haloalkylsulfonyl, O (C ₁ ~C ₄ haloalkyl), or -C (O) C ₁ ~C ₄ haloalkyl Or R ₂ is C ₃ -C ₆ cycloalkyl which may be mono- or polysubstituted with a substituent selected from the group consisting of halogen, cyano and C ₁ -C ₄ alkyl;
X ₁ is O, S or NR ₃ , wherein R ₃ is hydrogen, C ₁ -C ₄ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₄ alkoxy- C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl)
As well as the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of these compounds.

Compounds of formula I having at least one basic center are for example acid addition salts such as strong inorganic acids such as mineral acids such as perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid or hydrohalic acid. Acid addition salts with, strong organic carboxylic acids such as C ₁ -C ₄ alkane carboxylic acids which are unsubstituted or substituted with eg halogen, eg acetic acid, eg saturated or unsaturated dicarboxylic acids, eg oxalic acid, malonic acid , Succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids such as ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or acid addition salts with benzoic acid, or organic sulfonic acids such as unsubstituted C ₁ -C ₄ alkane are substituted with or is such as halogen at - or arylsulfonic acids, for example Tan - or acid addition salt with p- toluenesulfonic acid can be formed. Compounds of the formula I having at least one acidic group are, for example, salts with bases, such as inorganic salts, such as alkali metal or alkaline earth metal salts, such as sodium, potassium or magnesium salts, or ammonia or organic amines. Salts such as morpholine, piperidine, pyrrolidine, mono-, di- or tri-lower alkylamines such as ethyl-, diethyl-, triethyl- or dimethylpropylamine, or mono-, di- or trihydroxy-lower alkylamines For example, mono-, di- or triethanolamine can be formed.

  Alkyl groups present in the definition of substituents may be linear or branched, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert- Butyl, pentyl, hexyl, nonyl, decyl and their branched isomers. Alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkoxy, alkenyl and alkynyl groups are derived from the mentioned alkyl groups. Alkenyl and alkynyl groups can be mono- or polyunsaturated.

  Halogen is generally fluorine, chlorine, bromine or iodine. This applies correspondingly to halogens combined with other meanings such as haloalkyl or halophenyl.

  Haloalkyl groups preferably have a chain length of 1 to 6 carbon atoms. Haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1,1 -Difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl. In the context of the present invention, the haloalkyl group is preferably trichloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl.

  The alkoxy group preferably has a preferred chain length of 1 to 6 carbon atoms. Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy, as well as the isomeric pentyloxy and hexyloxy groups. In the context of the present invention, the alkoxy groups are preferably methoxy and ethoxy.

  The alkoxyalkyl group preferably has a chain length of 1 to 6 carbon atoms.

  Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.

Alkoxycarbonyl is, for example, (a C ₁ alkoxycarbonyl) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n- butoxycarbonyl, tert- butoxycarbonyl, n- pentoxycarbonyl or hexoxycarbonyl.

  Alkylsulfanyl is, for example, methylsulfanyl, ethylsulfanyl, propylsulfanyl, isopropylsulfanyl, butylsulfanyl, pentylsulfanyl, and hexylsulfanyl.

  Alkylsulfinyl is, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl, pentylsulfinyl and hexylsulfinyl.

  Alkylsulfonyl is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, pentylsulfonyl, and hexylsulfonyl.

  Cycloalkyl groups preferably have 3 to 6 ring carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

  Haloalkoxy groups preferably have a chain length of 1 to 4 carbon atoms. Haloalkoxy is, for example, difluoromethoxy, trifluoromethoxy or 2,2,2-trifluoroethoxy.

Haloalkylsulfanyl groups preferably have a chain length of 1 to 4 carbon atoms. Haloalkylsulfanyl is, for example, difluoromethylsulfanyl, trifluoromethylsulfanyl or 2,2,2-trifluoroethylsulfanyl. Similar considerations apply, for example, the trifluoromethyl sulfinyl, trifluoromethyl sulfonyl or 2,2,2 may be a trifluoroethyl sulfonyl, group C ₁ -C ₄ haloalkylsulfinyl and C ₁ -C ₄ haloalkylsulfonyl Is done.

  In the context of the present invention, “monosubstituted to polysubstituted” in the definition of substituents is typically monosubstituted to 7 times substituted, preferably monosubstituted to 5 times substituted, depending on the chemical structure of the substituent. More preferably, it means mono-, di- or tri-substitution.

  A free radical represents a methyl group.

  The compounds of formula I according to the invention also include hydrates that can be formed during salt formation.

Preferably, Q is always in 4-position, C ₃ -C ₆ cycloalkyl or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ cycloalkyl,, consisting of phenyl C ₃ -C ₆ cycloalkyl and halogen are mono- or polysubstituted by substituents selected from the group, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkyl sulfinyl, C ₁ -C ₄ haloalkylsulfonyl and -C (O) C _{1 ~C 4} group consisting haloalkyl A phenyl which may be mono- or poly-substituted with a substituent.

（式中、Ｒ₂およびＱが、上の式Ｉで定義されるとおりであり；Ｘａ₁が、Ｓ、ＳＯまたはＳＯ₂であり；およびＲａ₁が、メチル、エチル、ｎ−プロピル、ｉ−プロピルまたはシクロプロピルメチルである）
の化合物、ならびにそれらの化合物の農芸化学的に許容できる塩、立体異性体、鏡像異性体、互変異性体およびＮ−オキシドによって表される。式Ｉ−１の化合物の前記好ましい基において、Ｑが、好ましくは、Ｃ₃〜Ｃ₆シクロアルキル、またはシアノ、−Ｃ（Ｏ）ＯＨおよび−Ｃ（Ｏ）ＮＨ₂からなる群から選択される置換基で一置換されるＣ₃〜Ｃ₆シクロアルキルであり、特に、Ｑが、Ｃ₃〜Ｃ₆シクロアルキルまたは１−シアノシクロアルキルであり；Ｒ₂が、好ましくは、Ｃ₁〜Ｃ₄ハロアルキルであり；Ｘａ₁が、好ましくは、ＳまたはＳＯ₂であり、Ｒａ₁が、好ましくは、エチルである。式Ｉ−１の化合物の別の好ましい基において、Ｑが、好ましくは、Ｃ₃〜Ｃ₆シクロアルキルまたはシアノ、−Ｃ（Ｏ）ＯＨまたは−Ｃ（Ｏ）ＮＨ₂で一置換されるＣ₃〜Ｃ₆シクロアルキルであり、特に、Ｑが、Ｃ₃〜Ｃ₆シクロアルキルであり；Ｒ₂が、好ましくは、Ｃ₁〜Ｃ₄ハロアルキルスルファニル、Ｃ₁〜Ｃ₄ハロアルキルスルフィニルまたはＣ₁〜Ｃ₄ハロアルキルスルホニルであり；Ｘａ₁が、好ましくは、ＳまたはＳＯ₂であり、Ｒａ₁が、好ましくは、エチルである。 Preferred groups of compounds of formula I are those of formula I-1

Wherein R ₂ and Q are as defined in Formula I above; Xa ₁ is S, SO or SO ₂ ; and Ra ₁ is methyl, ethyl, n-propyl, i- Propyl or cyclopropylmethyl)
And the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of these compounds. In said preferred group of compounds of formula I-1, Q is preferably selected from the group consisting of C ₃ -C ₆ cycloalkyl, or cyano, —C (O) OH and —C (O) NH _2. C ₃ -C ₆ cycloalkyl monosubstituted with substituents, in particular Q is C ₃ -C ₆ cycloalkyl or 1-cyanocycloalkyl; R ₂ is preferably C ₁ -C ₄ Xa ₁ is preferably S or SO ₂ and Ra ₁ is preferably ethyl. In another preferred group of compounds of formula I-1, Q is preferably C ₃ -C ₆ cycloalkyl or cyano, C ₃ monosubstituted with —C (O) OH or —C (O) NH _2. -C ₆ cycloalkyl, in particular, Q is located at C ₃ -C ₆ cycloalkyl; R ₂ is preferably, C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkylsulfinyl or C ₁ -C ₄ haloalkylsulfonyl; Xa ₁ is preferably S or SO ₂ and Ra ₁ is preferably ethyl.

（式中、Ｒ₂およびＱが、上の式Ｉで定義されるとおりであり；Ｘａ₂が、Ｓ、ＳＯまたはＳＯ₂であり；およびＲａ₂が、メチル、エチル、ｎ−プロピル、ｉ−プロピルまたはシクロプロピルメチルである）
の化合物、ならびにそれらの化合物の農芸化学的に許容できる塩、立体異性体、鏡像異性体、互変異性体およびＮ−オキシドによって表される。式Ｉ−２の化合物のこの好ましい基において、Ｑが、好ましくは、Ｃ₃〜Ｃ₆シクロアルキルまたは１−シアノシクロアルキルであり；Ｒ₂が、好ましくは、Ｃ₁〜Ｃ₄ハロアルキルであり、Ｘａ₂が、好ましくは、ＳまたはＳＯ₂であり、Ｒａ₂が、好ましくは、エチルである。式Ｉ−２の化合物の別の好ましい基において、Ｑが、好ましくは、Ｃ₃〜Ｃ₆シクロアルキルであり；Ｒ₂が、好ましくは、Ｃ₁〜Ｃ₄ハロアルキルスルファニル、Ｃ₁〜Ｃ₄ハロアルキルスルフィニルまたはＣ₁〜Ｃ₄ハロアルキルスルホニルであり、Ｘａ₁が、好ましくは、ＳまたはＳＯ₂であり、Ｒａ₁が、好ましくは、エチルである。 Further preferred groups of compounds of formula I are those of formula I-2

Wherein R ₂ and Q are as defined in Formula I above; Xa ₂ is S, SO or SO ₂ ; and Ra ₂ is methyl, ethyl, n-propyl, i- Propyl or cyclopropylmethyl)
And the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of these compounds. In this preferred group of compounds of formula I-2, Q is preferably C ₃ -C ₆ cycloalkyl or 1-cyanocycloalkyl; R ₂ is preferably C ₁ -C ₄ haloalkyl; Xa ₂ is preferably S or SO ₂ and Ra ₂ is preferably ethyl. In another preferred group of compounds of formula I-2, Q is preferably C ₃ -C ₆ cycloalkyl; R ₂ is preferably C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkyl. Sulfinyl or C ₁ -C ₄ haloalkylsulfonyl, Xa ₁ is preferably S or SO ₂ , and Ra ₁ is preferably ethyl.

（式中、
Ｒ₂およびＱが、請求項１に記載の式Ｉで定義されるとおりであり；
Ｘａ₁₀が、Ｓ、ＳＯまたはＳＯ₂であり；および
Ｒａ₁₀が、メチル、エチル、ｎ−プロピル、ｉ−プロピルまたはシクロプロピルメチルである）
の化合物によって表される。 Further preferred groups of compounds of formula I are those of formula I-10

(Where
R ₂ and Q are as defined in formula I according to claim 1;
Xa ₁₀ is S, SO or SO ₂ ; and Ra ₁₀ is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl)
Represented by the compound

Preferred compounds of formula I-10 are those wherein Q is C ₃ -C ₆ cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ cycloalkyl, —C ( O) OH, -C (O) or a substituent selected from the group consisting of NH ₂ and phenyl which is monosubstituted or polysubstituted by C ₃ -C ₆ cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkyl sulfinyl, C ₁ -C ₄ haloalkylsulfonyl and -C (O) are those monosubstituted or polysubstituted may phenyl by C ₁ -C ₄ substituents selected from the group consisting of haloalkyl; especially, Q is, C ₃ -C ₆ cycloalkyl, or C ₃ -C ₆ is halogen, cyano, mono- or polysubstituted by C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ substituents selected from the group consisting of cycloalkyl and phenyl cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkyl sulfinyl, those C ₁ -C a ₄ haloalkylsulfonyl and -C (O) C ₁ ~C ₄ phenyl which may be mono- or polysubstituted by substituents selected from the group consisting of haloalkyl .

Even more preferred is formula I-10, wherein Q is C ₃ -C ₆ cycloalkyl, or a substitution selected from the group consisting of cyano, —C (O) OH and —C (O) NH ₂ A C ₃ -C ₆ cycloalkyl that is mono-substituted with a group.

（式中、
Ｒ₂およびＱが、請求項１に記載の式Ｉで定義されるとおりであり；
Ｘａ₂₀が、Ｓ、ＳＯまたはＳＯ₂であり；および
Ｒａ₂₀が、メチル、エチル、ｎ−プロピル、ｉ−プロピルまたはシクロプロピルメチルである）
の化合物によって表される。 Further preferred groups of compounds of formula I are those of formula I-20

(Where
R ₂ and Q are as defined in formula I according to claim 1;
Xa ₂₀ is S, SO or SO ₂ ; and Ra ₂₀ is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl)
Represented by the compound

Preferred compounds of formula I-20 can, Q consists of C ₃ -C ₆ cycloalkyl or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ cycloalkyl and phenyl, C ₃ -C ₆ cycloalkyl that is mono- or polysubstituted with a substituent selected from the group, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ halo alkoxy, C ₁ -C ₄ alkoxy, a C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkyl sulfinyl, C ₁ -C ₄ haloalkylsulfonyl and -C (O) C ₁ ~C ₄ group consisting haloalkyl Those that are phenyl that may be mono- or polysubstituted with selected substituents.

（式中、
Ａが、ＣＨまたはＮであり；
Ｘ₂が、ＳまたはＳＯ₂であり；
Ｘ₃が、Ｎ−（Ｃ₁〜Ｃ₄アルキル）であり；
Ｒ₄が、Ｃ₁〜Ｃ₄アルキルであり；
Ｒ₅が、Ｃ₁〜Ｃ₄ハロアルキルまたはＣ₁〜Ｃ₄ハロアルキルスルファニル、特に、Ｃ₁〜Ｃ₄ハロアルキルであり；および
Ｑ_aが、Ｃ₃〜Ｃ₆シクロアルキル、またはハロゲン、シアノ、Ｃ₁〜Ｃ₄アルキル、Ｃ₁〜Ｃ₄ハロアルキル、−Ｃ（Ｏ）ＯＨおよび−Ｃ（Ｏ）ＮＨ₂からなる群から選択される置換基で一置換または多置換されるＣ₃〜Ｃ₆シクロアルキルであり；特に、Ｑ_aが、Ｃ₃〜Ｃ₆シクロアルキル、またはハロゲン、シアノ、Ｃ₁〜Ｃ₄アルキルまたはＣ₁〜Ｃ₄ハロアルキルからなる群から選択される置換基で一置換または多置換されるＣ₃〜Ｃ₆シクロアルキルである）
の化合物によって表される。 Particularly preferred compounds of formula I are those of formula Ia-1

(Where
A is CH or N;
X ₂ is S or SO ₂ ;
X ₃ is N- (C ₁ -C ₄ alkyl);
R ₄ is C ₁ -C ₄ alkyl;
R ₅ is C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkylsulfanyl, especially C ₁ -C ₄ haloalkyl; and Q _a is C ₃ -C ₆ cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, -C (O) OH and -C (O) C ₃ ~C ₆ cycloalkyl that is mono- or polysubstituted by substituents selected from the group consisting of NH ₂ In particular, Q _a is mono- or poly-substituted with a substituent selected from the group consisting of C ₃ -C ₆ cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl or C ₁ -C ₄ haloalkyl C ₃ -C ₆ cycloalkyl)
Represented by the compound

In said preferred compounds of formula Ia-1, Q _a is preferably C ₃ -C ₆ cycloalkyl, or a substitution selected from the group consisting of cyano, —C (O) OH and —C (O) NH ₂ C ₃ -C ₆ cycloalkyl monosubstituted with groups; in particular, Q _a is preferably C ₃ -C ₆ cycloalkyl.

（式中、
Ａが、ＣＨまたはＮであり；
Ｘ₄が、Ｎ−（Ｃ₁〜Ｃ₄アルキル）であり；
Ｒ₆が、Ｃ₁〜Ｃ₄ハロアルキルまたはＣ₁〜Ｃ₄ハロアルキルスルファニル、特に、Ｃ₁〜Ｃ₄ハロアルキルであり；および
Ｑ_bが、Ｃ₃〜Ｃ₆シクロアルキル、またはシアノ、−Ｃ（Ｏ）ＯＨおよび−Ｃ（Ｏ）ＮＨ₂からなる群から選択される置換基で一置換されるＣ₃〜Ｃ₆シクロアルキルであり；特に、Ｑ_bが、Ｃ₃〜Ｃ₆シクロアルキルである）
の化合物によって表される。 Particularly preferred groups of compounds of formula I are those of formula Ia-2

(Where
A is CH or N;
X ₄ is N- (C ₁ -C ₄ alkyl);
R ₆ is C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkylsulfanyl, especially C ₁ -C ₄ haloalkyl; and Q _b is C ₃ -C ₆ cycloalkyl, or cyano, —C (O ) is OH and -C (O) C ₃ ~C ₆ cycloalkyl which is monosubstituted with a substituent selected from the group consisting of NH _2; particularly, Q _b is a C ₃ -C ₆ cycloalkyl)
Represented by the compound

（式中、Ａ、Ｒ₂およびＱが、上の式Ｉで定義されるとおりであり；Ｘａ₃が、Ｓ、ＳＯまたはＳＯ₂であり；Ｒａ₃が、メチル、エチル、ｎ−プロピル、ｉ−プロピルまたはシクロプロピルメチルである）
の化合物、ならびにそれらの化合物の農芸化学的に許容できる塩、立体異性体、鏡像異性体、互変異性体およびＮ−オキシドによって表される。式Ｉ−３の化合物の前記好ましい基において、Ｑが、好ましくは、Ｃ₃〜Ｃ₆シクロアルキルまたはシアノ、−Ｃ（Ｏ）ＯＨおよび−Ｃ（Ｏ）ＮＨ₂からなる群から選択される置換基で一置換されるＣ₃〜Ｃ₆シクロアルキルであり；Ｒ₂が、好ましくは、Ｃ₁〜Ｃ₄ハロアルキルまたはＣ₁〜Ｃ₄ハロアルキルスルファニルであり；Ｘａ₃が、好ましくは、ＳまたはＳＯ₂であり、およびＲａ₃が、好ましくは、エチルである。 Another preferred group of compounds of formula I is of formula I-3

Wherein A, R ₂ and Q are as defined in Formula I above; Xa ₃ is S, SO or SO ₂ ; Ra ₃ is methyl, ethyl, n-propyl, i -Propyl or cyclopropylmethyl)
And the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of these compounds. In said preferred groups of compounds of formula I-3, Q is preferably a C ₃ -C ₆ cycloalkyl or substitution selected from the group consisting of cyano, —C (O) OH and —C (O) NH ₂ C ₃ -C ₆ cycloalkyl monosubstituted with a group; R ₂ is preferably C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkylsulfanyl; Xa ₃ is preferably S or SO ₂ and Ra ₃ is preferably ethyl.

（式中、
Ａ、Ｒ₂およびＱが、請求項１に記載の式Ｉで定義されるとおりであり；
Ｘａ₃₀が、Ｓ、ＳＯまたはＳＯ₂であり；および
Ｒａ₃₀が、メチル、エチル、ｎ−プロピル、ｉ−プロピルまたはシクロプロピルメチルである）
の化合物によって表される。 Further preferred groups of compounds of formula I are those of formula I-30

(Where
A, R ₂ and Q are as defined in formula I according to claim 1;
Xa ₃₀ is S, SO or SO ₂ ; and Ra ₃₀ is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl)
Represented by the compound

Preferred compounds of formula I-30 are those in which Q is C ₃ -C ₆ cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ cycloalkyl, —C ( O) OH, -C (O) or a substituent selected from the group consisting of NH ₂ and phenyl which is monosubstituted or polysubstituted by C ₃ -C ₆ cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkyl sulfinyl, C ₁ -C ₄ haloalkylsulfonyl And —C (O) C ₁ -C ₄ haloalkyl is a phenyl that may be mono- or poly-substituted with a substituent selected from the group consisting of:

Even more preferred is the formula I-30, wherein Q is a C ₃ -C ₆ cycloalkyl, or a substitution selected from the group consisting of cyano, —C (O) OH and —C (O) NH ₂ A C ₃ -C ₆ cycloalkyl that is mono-substituted with a group.

（式中、
Ａが、ＣＨまたはＮ、好ましくは、Ｎであり；
Ｘ_2pが、ＳまたはＳＯ₂であり；
Ｘ_3pが、Ｎ−（Ｃ₁〜Ｃ₄アルキル）であり；
Ｒ_4pが、Ｃ₁〜Ｃ₄アルキルであり；
Ｒ_5pが、Ｃ₁〜Ｃ₄ハロアルキルまたはＣ₁〜Ｃ₄ハロアルキルスルファニル、好ましくは、Ｃ₁〜Ｃ₄ハロアルキルであり；および
Ｑ_apが、Ｃ₃〜Ｃ₆シクロアルキル、またはハロゲン、シアノ、Ｃ₁〜Ｃ₄アルキル、Ｃ₁〜Ｃ₄ハロアルキル、−Ｃ（Ｏ）ＯＨ、−Ｃ（Ｏ）ＮＨ₂およびフェニルからなる群から選択される置換基で一置換または多置換されるＣ₃〜Ｃ₆シクロアルキルである）
の化合物によって表される。 Particularly preferred compounds of formula I are those of formula Ia-3

(Where
A is CH or N, preferably N;
X _2p is S or SO ₂ ;
X _3p is N- (C ₁ -C ₄ alkyl);
R _4p is C ₁ -C ₄ alkyl;
R _5p is C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkylsulfanyl, preferably C ₁ -C ₄ haloalkyl; and Q _ap is C ₃ -C ₆ cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, -C (O) OH, -C (O) C 3 ~C be mono- or polysubstituted by substituents selected from the group consisting of NH ₂ and phenyl ₆ cycloalkyl)
Represented by the compound

In said preferred compounds of formula Ia-1, Q _ap is preferably C ₃ -C ₆ cycloalkyl, or a substitution selected from the group consisting of cyano, —C (O) OH and —C (O) NH ₂ C ₃ -C ₆ cycloalkyl monosubstituted with groups.

（式中、
Ａが、ＣＨまたはＮ、好ましくは、Ｎであり；
Ｘ_4pが、Ｎ−（Ｃ₁〜Ｃ₄アルキル）であり；
Ｒ_6pが、Ｃ₁〜Ｃ₄ハロアルキルまたはＣ₁〜Ｃ₄ハロアルキルスルファニル、好ましくは、Ｃ₁〜Ｃ₄ハロアルキルであり；および
Ｑ_bpが、Ｃ₃〜Ｃ₆シクロアルキル、またはシアノ、−Ｃ（Ｏ）ＯＨおよび−Ｃ（Ｏ）ＮＨ₂からなる群から選択される置換基で一置換されるＣ₃〜Ｃ₆シクロアルキルである）
の化合物によって表される。 Particularly preferred groups of compounds of formula I are those of formula Ia-4

(Where
A is CH or N, preferably N;
X _4p is N- (C ₁ -C ₄ alkyl);
R _6p is C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkylsulfanyl, preferably C ₁ -C ₄ haloalkyl; and Q _bp is C ₃ -C ₆ cycloalkyl, or cyano, —C ( O) OH and -C (O) with a substituent selected from the group consisting of NH ₂ is a C ₃ -C ₆ cycloalkyl which is monosubstituted)
Represented by the compound

Even more preferred is the formula Ia-4
(Where
A is N;
X _4p is N- (C ₁ -C ₄ alkyl);
R _6p is C ₁ -C ₄ haloalkyl; and Q _bp is C ₃ -C ₆ cycloalkyl, or C ₃ -C ₆ cycloalkyl monosubstituted with cyano).

In an excellent group of compounds of formula I
R ₁ is C ₁ -C ₄ alkyl;
R ₂ is C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkylsulfanyl;
X is S or SO ₂ ;
X ₁ is N- (C ₁ -C ₄ alkyl);
A is N;
Q is, C ₃ -C ₆ cycloalkyl, or cyano, with -C (O) OH or -C (O) C ₃ ~C ₆ cycloalkyl which is monosubstituted with a substituent selected from the group consisting of NH _2, Yes; and Q can be in the 3 or 4 position; and the N-oxide of said superior compound of formula I.

  The process according to the invention for preparing the compounds of the formula I is in principle carried out by methods known to those skilled in the art. The following method illustrates the preparation of a compound of formula I where Q is in the 4-position. Compounds of formula I (wherein Q is in position 3) can be prepared analogously.

More particularly, the compound of formula I may be a compound of formula II of formula III where _Xb1 is halogen, preferentially chlorine, bromine or iodine, or a sulfonate such as, for example, trifluoromethanesulfonate. Y _b1 can be a functional group derived from boron, for example B (OH) ₂ or B (OR _b1 ) ₂ , where R _b1 can be a C ₁ -C ₆ alkyl group, Or by reacting the two groups OR _b1 together with a boron atom with a compound (which can form a 5- or 6-membered ring such as, for example, pinacol boronate) (as shown in Scheme 1) (See Suzuki Cross Coupling, eg Tetrahedron Letters, 43 (39), 6987-6990; 2002). In Formulas II and III, A, X ₁ , R ₁ , R ₂ , X and Q are as described in Formula I. The reaction is preferably carried out under an inert atmosphere with a solvent (such as toluene, 1,2-dimethoxy-ethane DME, tetrahydrofuran or dioxane) or for example 1,2-dimethoxyethane (or dioxane, toluene or tetrahydrofuran) and water. Palladium-based catalysts such as tetrakis (triphenylphosphine) palladium (0), bis (triphenylphosphine) in the presence of a base such as sodium carbonate, tripotassium phosphate or cesium fluoride in a solvent mixture such as ) Palladium (II) dichloride, chloro (2-dicyclohexylphosphino-2 ', 4', 6'-triisopropyl-1,1'-biphenyl) [2- (2'-amino-1,1'-biphenyl) ] Palladium (II) (XPhos paradacycle), (1, 'Bis (diphenylphosphino) - ferrocene) dichloropalladium - dichloromethane (1: 1 complex) or palladium acetate and a phosphine ligand (e.g., triphenylphosphine or tricyclohexylphosphine) can be catalyzed by. The reaction temperature can preferentially range from ambient temperature to the boiling point of the reaction mixture, or the heating can be performed under microwave irradiation.

Alternatively, the compound of formula II, wherein X _b1 can be halogen, preferentially chlorine, bromine or iodine, or a sulfonate such as trifluoromethanesulfonate, is optionally a zinc halide, etc. additives formula III in the presence of (in the formula, Y _b1 is a magnesium halide group, such as -MgBr) which may be reacted with a compound of (Kumada cross-coupling) (Journal of Organic Chemistry, 75 (19) 6677-6680; 2010). The reaction may be catalyzed by a palladium-based catalyst or may include a nickel-based catalyst such as 1,3-bis (diphenylphosphino) propane nickel dichloride (dppp) NiCl ₂ .

Formula II, for example as shown in Synthetic Communications, 28 (2), 225-232; 1998, wherein X _b1 is halogen, preferentially chlorine, bromine or iodine, or such as, for example, trifluoromethanesulfonate. Also known is the reaction (Negishi coupling) of a compound of formula III (which can be a sulfonate) with a compound of formula III where Y _b1 is a zinc halide group such as —ZnBr. The reaction is preferably carried out in an inert atmosphere, for example in a solvent such as 1,2-dimethoxyethane, dioxane, toluene or tetrahydrofuran, optionally with a phosphine additive (eg 2-dicyclohexyl-phosphino- In the presence of 2 ′, 6′-dimethoxy-biphenyl S-PHOS), for example, (1,1′bis (diphenylphosphino) -ferrocene) dichloropalladium Pd (dppf) Cl ₂ or bis (triphenylphosphine) palladium (II) It can be catalyzed by a palladium-based catalyst such as dichloride. The reaction temperature can preferentially range from ambient temperature to the boiling point of the reaction mixture.

The compound of formula I may also be a compound of formula IV wherein X _b2 is halogen, preferentially chlorine, bromine or iodine, or a sulfonate such as trifluoromethanesulfonate, where Y _b2 is Can be a functional group derived from boron, for example B (OH) ₂ or B (OR _b2 ) ₂ , where R _b2 can be a C ₁ -C ₆ alkyl group or two groups OR _b2 can be made (as shown in Scheme 2) by reacting with a boron atom and a compound that can form a 5- or 6-membered ring such as, for example, a pinacol boronate ester. In Formulas IV and V, A, X ₁ , R ₁ , R ₂ , X and Q are as described in Formula I. The reaction is preferably carried out in an inert atmosphere with a solvent (such as toluene, 1,2-dimethoxy-ethane DME, tetrahydrofuran or dioxane) or a mixture of, for example, 1,2-dimethoxyethane and water, or dioxane and water. In a solvent mixture such as a mixture, a palladium-based catalyst such as tetrakis (triphenylphosphine) palladium (0), bis (triphenylphosphine) in the presence of a base such as sodium carbonate, tripotassium phosphate or cesium fluoride. It can be catalyzed by palladium (II) dichloride or (1,1′bis (diphenylphosphino) -ferrocene) dichloropalladium-dichloromethane (1: 1 complex). The reaction temperature can preferentially range from ambient temperature to the boiling point of the reaction mixture, or the heating can be performed under microwave irradiation.

A compound of formula I-a3, wherein A, R ₁ , R ₂ , X ₁ and Q have the values defined in formula I and X is —SO ₂ — is a compound of formula I-a2 ( Wherein A, R ₁ , R ₂ , X ₁ and Q have the values defined in Formula I, and X is —SO—. The reaction can be, for example, a peracid such as peracetic acid or m-chloroperbenzoic acid, or a hydroperoxide such as hydrogen peroxide or tert-butyl hydroperoxide, or monoperoxodisulfate or potassium permanganate. It can be performed using a reagent such as an inorganic oxidizing agent. Similarly, compounds of formula I-a2 wherein A, R ₁ , R ₂ , X ₁ and Q have the values defined in formula I and X is —SO— are described above. Of compounds of formula I-a1 under the conditions similar to those in which A, R ₁ , R ₂ , X ₁ and Q have the values defined in formula I and X is —S— It can be prepared by oxidation. These reactions can be performed in various organic solvents (eg, dichloromethane) or aqueous solvents that meet these conditions, depending on the temperature from below 0 ° C. to the boiling point of the solvent system. Conversion of compounds of formula 1-a1 to compounds of formulas 1-a2 and 1-a3 is represented in Scheme 3.

The compound of formula I-a1 can also be a compound of formula VI where formula A is a compound of formula VII where A, R ₁ , R ₂ , X ₁ and Q have the values defined in formula I, and X is sulfur, (M is a metal or non-metal cation) and can be prepared (Scheme 4). In Scheme 4, the cation M is assumed to be monovalent, but multivalent cations attached to two or more S—R ₁ groups can also be envisaged. Preferred cations are for example lithium, sodium, potassium or cesium. For this transformation to work, Xb ₃ is a leaving group such as, for example, fluorine, chlorine, bromine or iodine, or aryl sulfonate or alkyl sulfonate, but many other leaving groups are contemplated. obtain. The reaction can be carried out at a temperature below 0 ° C. or up to the boiling point of the reaction mixture, preferably in an aprotic solvent such as N, N-dimethylformamide or acetonitrile.

（式中、
Ａ、Ｑ、Ｘ₁およびＲ₂が、請求項１に記載の式Ｉで定義されるとおりであり；および
Ｘｂ₃₀がハロゲンである）
の化合物は、新規であり、特に、本発明に係る化合物の調製のために開発される。したがって、式ＶＩ−ａの化合物は、本発明のさらなる対象である。 Formula VI-a

(Where
A, Q, X ₁ and R ₂ are as defined in formula I of claim 1; and Xb ₃₀ is halogen)
These compounds are novel and are especially developed for the preparation of the compounds according to the invention. Accordingly, compounds of formula VI-a are a further subject of the present invention.

Formula VI wherein Xb ₃ is a leaving group such as, for example, fluorine, chlorine, bromine or iodine, or an aryl sulfonate or alkyl sulfonate such as trifluoromethanesulfonate, or any other similar leaving group Is a compound of formula VIII wherein X _b4 is halogen, preferentially chlorine, bromine or iodine, or a sulfonate such as trifluoromethanesulfonate, most preferably bromine or It can be iodine and Y _b4 can be a functional group derived from boron, for example B (OH) ₂ or B (OR _b4 ) ₂ , where R _b4 is a C ₁ -C ₆ alkyl group. by and obtain or two groups oR _b4 is, together with the boron atom, for example to form a 5-membered or 6-membered ring such as pinacol boronic ester) compounds with anti It may be prepared by (Scheme 5). In formulas VI, VIII and IX, A, X ₁ , R ₂ and Q are as described in formula I. The reaction is preferably carried out in an inert atmosphere with a solvent (such as toluene, 1,2-dimethoxy-ethane DME, tetrahydrofuran or dioxane) or a mixture of, for example, 1,2-dimethoxyethane and water, or dioxane and water. In a solvent mixture such as a mixture, a palladium-based catalyst such as tetrakis (triphenyl-phosphine) palladium (0), bis (triphenylphosphine) in the presence of a base such as sodium carbonate, tripotassium phosphate or cesium fluoride. ) Palladium (II) dichloride or (1,1′bis (diphenyl-phosphino) -ferrocene) dichloropalladium-dichloromethane (1: 1 complex). The reaction temperature can preferentially range from ambient temperature to the boiling point of the reaction mixture, or the heating can be performed under microwave irradiation.

Alternatively, a compound of formula VIII, wherein X _b4 can be halogen, preferentially chlorine, bromine or iodine, or a sulfonate such as trifluoromethanesulfonate, is optionally a zinc halide, etc. additives formula IX in the presence of (in the formula, the Y _b4, a magnesium halide group, such as -MgBr) which may be reacted with a compound of (Kumada cross-coupling) (Journal of Organic Chemistry, 75 (19) 6677-6680; 2010). The reaction may be catalyzed by a palladium-based catalyst or may include a nickel-based catalyst such as 1,3-bis (diphenylphosphino) propane nickel dichloride (dppp) NiCl ₂ .

Formula VIII, where X _b4 is halogen, preferentially chlorine, bromine or iodine, or such as, for example, trifluoromethanesulfonate, as shown for example in Synthetic Communications, 28 (2), 225-232; 1998 Also known is the reaction (Negishi coupling) with a compound of the formula IX (wherein Y _b4 is a zinc halide group such as —ZnBr), which can be a sulfonate as such. The reaction is preferably carried out in an inert atmosphere, for example in a solvent such as 1,2-dimethoxyethane, dioxane, toluene or tetrahydrofuran, optionally with a phosphine additive (eg 2-dicyclohexyl-phosphino- In the presence of 2 ′, 6′-dimethoxy-biphenyl S-PHOS), for example, (1,1′bis (diphenylphosphino) -ferrocene) dichloropalladium Pd (dppf) Cl ₂ or bis (triphenylphosphine) palladium (II) It can be catalyzed by a palladium-based catalyst such as dichloride. The reaction temperature can preferentially range from ambient temperature to the boiling point of the reaction mixture.

In an alternative method shown in Scheme 6, the compound of formula VI may also be of the formula X (wherein Xb ₃ is, for example, fluorine, chlorine, bromine or iodine, or an aryl sulfonate or sulfonic acid such as trifluoromethanesulfonate A compound of the formula XI, wherein X _b5 is halogen, preferentially chlorine, bromine or iodine, or such as trifluoromethane, is a leaving group such as alkyl, or any other similar leaving group A sulfonate such as sulfonate, most preferably bromine or iodine, where Y _b5 can be a functional group derived from boron, for example B (OH) ₂ or B (OR _b5 ) ₂ , where , R _b5 is be a C ₁ -C ₆ alkyl group, or two groups oR _b5, together with the boron atom, such as a pinacol boronate ester 5 Or it may be prepared by reacting a 6-membered compounds of ring capable of forming). In formulas VI, X and XI, A, X ₁ , R ₂ and Q are as described in formula I. The reaction is preferably carried out in an inert atmosphere with a solvent (such as toluene, 1,2-dimethoxy-ethane DME, tetrahydrofuran or dioxane) or a mixture of, for example, 1,2-dimethoxyethane and water, or dioxane and water. In a solvent mixture such as a mixture, a palladium-based catalyst such as tetrakis (triphenylphosphine) palladium (0), bis (triphenylphosphine) in the presence of a base such as sodium carbonate, tripotassium phosphate or cesium fluoride. It can be catalyzed by palladium (II) dichloride or (1,1′bis (diphenylphosphino) -ferrocene) dichloropalladium-dichloromethane (1: 1 complex). The reaction temperature can preferentially range from ambient temperature to the boiling point of the reaction mixture, or the heating can be performed under microwave irradiation.

The compounds of formula I can also be obtained under various formal dehydration conditions using compounds of formula XIII and compounds of formula XIV wherein A, R ₁ , R ₂ , X, X ₁ and Q have the values defined in formula I. Can be prepared (Scheme 7). These methods are known to those skilled in the art or, for example, International Publication No. 2009/131237, International Publication No. 2011/043404, International Publication No. 2011/040629, International Publication No. 2010/125985, International Publication No. 2012. No. 0886848, International Publication No. 2013/018928, International Publication No. 2013/191113, International Publication No. 2013/180193, and International Publication No. 2013/180194. Such methods are well known, for example WO 2011/040629 or WO 2009131237 (X ₁ is oxygen), WO 2011088990 No. or Inorg. Chimica Acta, 358 (9), 2701-2710; 2005 (X ₁ is sulfur) and J. Am. Am. Chem. Soc. 132 (5), 1545-1557, 2010 or WO 20080081968 (where X ₁ is NR ₃ ). Compounds of formula XIII are commercially available or are described, for example, in WO 2012/0886848.

The process illustrating the reaction of a compound of formula XIII with a compound of formula XIV to obtain a compound of formula I is summarized in more detail in Scheme 8.

Compounds of formula XIV (wherein A, R ₁ , X and Q are as described above) are known to those skilled in the art, for example described in Tetrahedron, 61 (46), 10827-10852, 2005 The method activates to compounds of formula XIV-a (Scheme 8). For example, a compound in which X ₀ is chlorine is, for example, oxalyl chloride or in the presence of a catalytic amount of DMF in an inert solvent such as methylene chloride or THF at a temperature of 20 ° C. to 100 ° C., preferably 25 ° C. Formed by treatment with thionyl chloride. Optionally, treatment of XIV-a with a compound of formula XIII (wherein R ₂ and X ₁ are as described in formula I) in the presence of a base, such as triethylamine or pyridine, may be carried out according to formula XV Results in the compound. Alternatively, the compound of formula I can be reacted with the active species XIV-a (at a temperature of 50-180 ° C., optionally in the presence of a base such as triethylamine, in an inert solvent such as pyridine or tetrahydrofuran (THF). By treatment of a compound of formula XIV with dicyclohexylcarbodiimide (DCC) or 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC) to obtain X ₀ is X ₀₁ and X ₀₂ respectively. Can be prepared. The compound of formula XV thus obtained is then subjected to an acid catalyst, such as methanesulfone, in an inert solvent such as N-methylpyrrolidone or xylene at a temperature of 25 to 180 ° C., preferably 130 to 170 ° C. In the presence of acid, or para-toluenesulfonic acid p-TsOH, may optionally be converted to a compound of formula I by dehydration under microwave irradiation, for example by heating the compound. Such a process has already been described in WO 2010/125985. Alternatively, the compound of formula XV can be prepared using formula I (wherein X ₁ is O) using triphenylphosphine, di-isopropyl azodicarboxylate in an inert solvent such as THF at a temperature of 25-50 ° C. Can be converted to Such Mitsunobu conditions for such conversion have already been described (see WO 2009/131237).

（式中、ＡおよびＱが式Ｉについて定義される値を有する）
の化合物を、例えば塩化オキサリルもしくは塩化チオニルまたはカルボジイミド試薬のような活性剤と反応させて、活性化種ＸＶＩ−ａを生成した後、式ＸＩＩＩ（式中、Ｒ₂およびＸ₁が式Ｉに記載されるとおりである）の化合物との反応によって調製され得る。式ＸＶＩＩの中間化合物は、単離され得るが、優先的に、化合物ＸＶの、式Ｉの化合物への変換について上述されるのと同様の方法で式ＶＩの化合物へと転化される。 In a similar method (Scheme 9), formula VI where Xb ₃ is, for example, fluorine, chlorine, bromine or iodine, or aryl sulfonate or alkyl sulfonate such as trifluoromethanesulfonate, or any other similar A leaving group such as a leaving group) is a compound of formula XVI

(Wherein A and Q have the values defined for formula I)
Is reacted with an activator such as oxalyl chloride or thionyl chloride or a carbodiimide reagent to produce activated species XVI-a, wherein R ₂ and X ₁ are described in Formula I As is). The intermediate compound of formula XVII can be isolated but preferentially converted to the compound of formula VI in a manner similar to that described above for the conversion of compound XV to the compound of formula I.

式ＸＶＩＩＩの化合物、または式ＸＶＩＩＩの化合物の活性化形態ＸＶＩＩＩ−ａ（式中、Ａが、炭素または窒素であり、Ｘ_b3が、例えばフッ素、塩素、臭素またはヨウ素、またはトリフルオロメタンスルホネートなどのスルホン酸アリールもしくはスルホン酸アルキルのような脱離基であり、Ｘ_b4が、ハロゲン、優先的に、塩素、臭素またはヨウ素、または例えばトリフルオロメタンスルホネートのようなスルホネート、最も好ましくは、臭素またはヨウ素であり得る）を式ＸＩＩＩ（式中、Ｘ₁およびＲ₂が式Ｉにおいて定義されるとおりである）の化合物と反応させることにより、スキーム１０に記載されるように調製され得る。式ＸＩＸの中間化合物は、単離され得るが、優先的に、上述されるのと同様の方法で式ＶＩＩＩの化合物へと転化される（ＸＶの化合物の、式Ｉの化合物への変換）。 In a manner similar to that described above, the compound of formula VIII is

A compound of formula XVIII, or an activated form XVIII-a of a compound of formula XVIII, wherein A is carbon or nitrogen and X _b3 is a sulfone such as, for example, fluorine, chlorine, bromine or iodine, or trifluoromethanesulfonate A leaving group such as an aryl or alkyl sulfonate and X _b4 is halogen, preferentially chlorine, bromine or iodine, or a sulfonate such as trifluoromethanesulfonate, most preferably bromine or iodine Can be prepared as described in Scheme 10 by reacting with a compound of formula XIII, wherein X ₁ and R ₂ are as defined in formula I. The intermediate compound of formula XIX can be isolated but preferentially converted to the compound of formula VIII in the same manner as described above (conversion of the compound of XV to the compound of formula I).

A compound of formula XXI is of formula XX wherein A is CH or nitrogen and X _b3a is an aryl sulfonate or alkyl sulfonate such as nitro, fluorine, chlorine, bromine or iodine, or trifluoromethanesulfonate, for example. A compound of formula VII, wherein X _b4 is halogen, preferentially chlorine, bromine or iodine, or a sulfonate such as, for example, trifluoromethanesulfonate, most preferably bromine or iodine. It can be prepared as described in Scheme 10a by reacting with a compound of the formula (wherein R ₁ is as defined in Formula I and M is a metal or non-metal cation). In Scheme 10a, the cation M is assumed to be monovalent, but multivalent cations combined with two or more S—R ₁ groups can also be envisaged. Preferred cations are for example lithium, sodium, potassium or cesium. The reaction may be carried out in a preferably polar aprotic solvent such as THF, N, N-dimethylformamide or MeCN at temperatures from -78 ° C to the boiling point of the reaction mixture. Compounds of formula XVIII-c can be prepared according to formula XXI under acidic conditions (eg HCl or H ₂ SO ₄ ) or basic conditions (eg NaOH or KOH) as described in Scheme 10a under conditions known to those skilled in the art. Can be prepared by hydrolysis of the compound. Compounds of formula II-a1 are as compound or which in the activated form XVIII-d and Formula XIII (formula for a compound of formula XVIII-c of the formula XVIII-c, X ₁ and R ₂ are as defined in formula I ) Can be prepared as described in Scheme 10a. Intermediate compounds of formula XXII can be isolated but preferentially converted to compounds of formula II-a1 in the same manner as described above (conversion of compound XV to compounds of formula I) . In compounds of formula XXI, XVIII-c, XVIII-d, XXII and II-a1, X can be S, SO or SO ₂ (when X is SO, the compound of formula II-a1 is of formula II or if X is SO _2, compounds of formula II-a1 is made to a compound of formula II-a3;; into compounds of -a2 see scheme 12). Suitable oxidized forms of the sulfur atom in the compounds of formula XXI, XVIII-c, XVIII-d, XXII and II-a1 where X is SO or SO ₂ are formula XXI, XVIII-c, It can be prepared by oxidation of compounds of XVIII-d, XXII and II-a1, where X is S. The reaction may be a peracid such as peracetic acid or m-chloroperbenzoic acid, or a hydroperoxide such as hydrogen peroxide or tert-butyl hydroperoxide, or monoperoxydisulfate or potassium permanganate. Inorganic oxidants, preferentially, can be performed using reagents such as meta-chloro-perbenzoic acid as described above.

Alternatively, compounds of formula XVIII-c, where X is S, SO or SO ₂ can be prepared by methods analogous to those described in the literature (Scheme 10b). For example, a compound of formula XVIII-c wherein X is S is a condition known to those skilled in the art (R ₁ is as defined in formula I, A is N or CH, and X _b4 is halogen, preferentially chlorine, bromine or iodine, or a sulfonate such as, for example, trifluoromethanesulfonate, most preferably bromine or iodine, under formula XXIV where R _LG is C ₁ ~C can be prepared by saponification of a compound of ₄ alkyl as).

A compound of formula XXIV where R _LG is C ₁ -C ₄ alkyl is a compound of formula VII where R ₁ is as defined in formula I and M is a metal Or a non-metal cation reagent M-S-R ₁ for formula XXIII where Xb ₃ a is for example nitro, fluorine, chlorine, bromine or iodine, or aryl sulfonate or sulfonic acid such as trifluoromethanesulfonate Leaving groups such as alkyl and R _LG is C ₁ -C ₄ alkyl). Such a process involving, for example, sodium methane- or ethanethiolate as the reagent M—S—R ₁ is well known and has already been described, for example, in WO 2014/152738. The compound of formula XXIV is oxidized to the compound of formula XXIV-a using methods known to those skilled in the art as described, for example, in Scheme 12, followed by formula XVIII-c where X is SO or SO ₂ ). Alternatively, a compound of formula XXIV is first saponified to a compound of formula XVIII-c, where X is S, and then XVIII-c, where X is SO or SO ₂ ). Compounds of formula XXIII are commercially available or are described in WO 2012/086848.

Changing the order of the reaction conditions described above also converts the compounds of formula XVIII-c, or their activated forms XVIII-d, to useful compounds of formula XXIV, or their oxidized forms XXIV-a. Can be possible. This is shown in Scheme 10c.

As described in Scheme 10c, ester compounds of formula XXIV, wherein X is S and R _LG is C ₁ -C ₄ alkyl, are optionally acid (such as sulfuric acid) An alcohol of the formula R _LG OH (where R _LG is C ₁ -C ₄ alkyl) in the presence or optionally in the presence of an activator such as, for example, oxalyl chloride (COCl) ₂ Can be prepared from the corresponding carboxylic acid compound of formula XVIII-c, where X is S. Such esterification methods are well known to those skilled in the art and are described in the literature. The compound of formula XXIV can be oxidized to the compound of formula XXIV-a as illustrated in Scheme 10b. The definition of substituents in the compounds of formulas XVIII-c, XVIII-d, XXIV and XXIV-a has been described above.

A compound of formula II-a1 where X is sulfur is a compound of formula VIII where A, R ₂ and X ₁ are as defined in formula I and X _b3 is, for example, fluorine, Chlorine, bromine or iodine, or aryl sulfonates or alkyl sulfonates such as trifluoromethanesulfonate, preferentially leaving groups such as fluorine or chlorine, and X _b4 is halogen, preferentially chlorine, bromine or iodine, Or a sulfonate, such as trifluoromethanesulfonate, most preferably bromine or iodine, of formula VII where R ₁ is as defined in formula I and M is a metal or non-metal cation (Scheme 11). In Scheme 11, the cation M is assumed to be monovalent, but multivalent cations attached to two or more S—R ₁ groups can also be envisaged. Preferred cations are for example lithium, sodium, potassium or cesium. The reaction can be carried out at a temperature below 0 ° C. or below the boiling point of the reaction mixture, preferably in a polar aprotic solvent.

Formula II-a3 wherein A, R ₁ , R ₂ and X ₁ have the values defined in Formula I, X is —SO ₂ —, X _b4 is halogen, preferentially Compounds of chlorine, bromine or iodine, or sulfonates such as trifluoromethanesulfonate, have the formula II-a2 where A, R ₁ , R ₂ and X ₁ have the values defined in formula I And X is —SO— and X _b4 is halogen, preferentially chlorine, bromine or iodine, or a sulfonate such as trifluoromethanesulfonate, for example. ). The reaction can be a peracid such as peracetic acid or m-chloroperbenzoic acid, or a hydroperoxide such as hydrogen peroxide or tert-butyl hydroperoxide, or a monoperoxodisulfate or potassium permanganate. It can be carried out using an inorganic oxidant, preferentially a reagent such as meta-chloroperbenzoic acid. Similarly, Formula II-a2 wherein A, R ₁ , R ₂ and X ₁ have the values defined in Formula I, X is —SO—, X _b4 is halogen, preferentially Or a compound of chlorine, bromine or iodine, or a sulfonate such as trifluoromethanesulfonate, is of formula II-a1 where A, R ₁ , R ₂ and X ₁ are defined in formula I And X _b4 is a halogen, preferentially chlorine, bromine or iodine, or a sulfonate such as trifluoromethanesulfonate. These reactions can be carried out in various organic or aqueous solvents that meet these conditions, with temperatures below 0 ° C. and below the boiling point of the solvent system.

Many compounds of formula V and XI (wherein Q has the value defined in formula I and X _b2 and X _b5 are as defined above) are either commercially available or in the literature Are available to those skilled in the art by methods similar to those described in.

Many compounds of formula III are commercially available or can be prepared by one skilled in the art. Many chemical transformations well known to those skilled in the art, for example using a strong base (Step A) such as butyl lithium or lithium diisopropylamide or (i-PrMgCl, LiCl) to name a few (Scheme 13) Hydrogen extraction in a compound of formula III-a where Zb ₁ is hydrogen, followed by, for example, formula III-b with trialkyl borate, where Zb ₂ is, for example, Li ⁺ or The reaction of a metallated intermediate (step B), which is a metal such as MgCl ⁺ , can be used to obtain boronic acid derivatives of formula III starting from various readily available starting materials. . Another method for obtaining organometallic intermediates of formula III-b is from compounds of formula III-a where Zb ₁ is chlorine, bromine or iodine, such as butyl lithium or organomagnesium compounds. Metal-halogen exchange using various organometallic species (step C) or direct metallization using a metal such as magnesium.

(Wherein, Zb ₁ is chlorine, bromine, iodine or a triflate) Formula III-a introduction of pinacol borate (Pinacolborate) functional groups by palladium catalyzed reaction with bi spinner call diborane in the compound of, specifically Another common (Scheme 13, step D). In the compounds of formula III-a, III-b and III in scheme 13, Q has the value defined for formula I. One skilled in the art will be able to select an appropriate preparation method to obtain a compound of formula III from III-a, depending on the value of Q.

  Exactly the same method of preparation as described in Scheme 13 can be applied to the synthesis of intermediates of formula IX.

A compound of formula IV (wherein A, X, X ₁ , R ₁ and R ₂ are as described in formula I) is a compound of formula II (Scheme 14) wherein A, X, X ₁ , R ₁ and R ₂ are as described in Formula I). Indeed, a compound of formula II where Xb ₁ is chlorine, bromine or iodine is treated with an organometallic species such as, for example, butyllithium or an organomagnesium compound and by metal-halogen exchange, Intermediate compounds of formula II-a, where Zb ₃ is as defined in the scheme, can be produced. This reaction is preferentially performed at low temperature (−120 ° C. to 0 ° C., preferentially −110 ° C. to −60 ° C.) in an anhydrous aprotic solvent such as THF. The intermediate organometallic compound of formula II-a is preferably converted to a compound of formula IV by reaction with boronate compound B (OR _b2 ) ₃ , where R _b2 is a C ₁ -C ₆ alkyl group. And converted directly. Depending on the nature of the boronate, reaction conditions and workup conditions, the boronic acid IV (wherein Yb ₂ is —B (OH) ₂ or a dialkyl boronate IV and Yb ₂ is —B ( OR _b2 ) ₂ ) may be formed.

である）を生成するこの反応は、塩基、優先的に酢酸カリウムＫＯＡｃなどの弱塩基の存在下において非プロトン性溶媒中で行われ得る。パラジウムｄｐｐｆジクロリドまたはＰｄ（ｄｐｐｆ）Ｃｌ₂としても知られている［１，１’−ビス（ジフェニルホスフィノ）フェロセン］ジクロロパラジウム（ＩＩ）が、このタイプの反応のための一般的な触媒である。反応の温度は、好ましくは、０℃から反応混合物の沸点の間に含まれる。

Bispinacol diborane in compounds of formula II wherein A, X, X ₁ , R ₁ and R ₂ are as described in formula I and Xb ₁ is chlorine, bromine, iodine or triflate The introduction of a pinacol borate functional group by palladium catalyzed reaction with B ₂ Pin ₂ is another common approach. Cyclic boronate IV where Yb ₂ is

This reaction can be carried out in an aprotic solvent in the presence of a base, preferentially a weak base such as potassium acetate KOAc. [1,1′-bis (diphenylphosphino) ferrocene] dichloropalladium (II), also known as palladium dppf dichloride or Pd (dppf) Cl ₂ , is a common catalyst for this type of reaction. . The temperature of the reaction is preferably comprised between 0 ° C. and the boiling point of the reaction mixture.

Wherein I (wherein, Q is, C ₃ -C ₆ cycloalkyl or halogen, cyano, C ₁ -C ₄ haloalkyl, and C ₃ to be mono- or polysubstituted by substituents selected from the group consisting of phenyl, compounds of -C ₆ cycloalkyl) can be prepared by the methods described above (especially, in the formula I (wherein, Q is cyclopropyl) compounds of the described made in scheme 1, a cyclopropyl - Can be prepared by the Suzuki reaction with boronic acid). In the special case of compounds of formula I where Q is C ₃ -C ₆ cycloalkyl substituted with cyano (eg compound Iaa) and C ₁ -C ₄ haloalkyl (eg compound Iad) Can be prepared by the method shown in Scheme 15.

As shown in Scheme 15, optionally, zinc fluoride (with zinc ligand (eg, xanthophos) in an inert solvent such as N, N-dimethylformamide DMF at a temperature of 100-180 ° C. under microwave heating. II) Formula II with trimethylsilyl-acetonitrile TMSCN in the presence of a palladium (0) catalyst such as ZnF ₂ and tris (dibenzylideneacetone) dipalladium (0) -chloroform adduct (Pd ₂ (dba) ₃ ) In which X is S, SO or SO ₂ (especially SO ₂ ), wherein A, X ₁ , R ₁ and R ₂ are as defined above, where Xb ₁ is For example, chlorine, bromine or iodine (preferably bromine), or aryl sulfonates such as trifluoromethanesulfonate or Treatment of a compound of the sulfonic acid is a leaving group such as alkyl), (wherein, X is, S, SO, or SO ₂ (in particular, SO ₂₎ Formula Iab compound of a) is obtained. Such chemical reactions are described in the literature, eg Org. Lett. 16 (24), 6314-6317, 2014. A compound of formula Iab is prepared from sodium hydride, potassium carbonate K ₂ CO ₃ , or cesium carbonate Cs _{2 in} an inert solvent such as N, N-dimethylformamide DMF, acetone, or acetonitrile at a temperature of 0-120 ° C. Formula XXXII in the presence of a base such as CO ₃ , wherein Qx is a direct bond or (CH ₂ ) _n and n is 1, 2 or 3, wherein Xb ₁₀ is Treated with a compound of a halogen (which is a leaving group such as chlorine, bromine or iodine), and is of formula Iaa, wherein X is S, SO or SO ₂ (especially SO ₂ ); Where A, X ₁ , R ₁ and R ₂ are as defined above, where Qx is a direct bond or (CH ₂ ) _n and n is 1, 2 or 3) is obtained. Alternatively, the compound of formula Iaa can be synthesized at a temperature of 30-80 ° C. with a ligand such as BINAP and a strong base such as lithium hexamethyldisilazane LiHMDS in an inert solvent such as tetrahydrofuran THF, such as Pd ₂ (dba) ₃ . It can be prepared directly from a compound of formula II by treatment with a compound of formula XXXIII (wherein Qx is as described in XXII) in the presence of a catalyst. Such chemical reactions are described, for example, in J. Org. Am. Chem. Soc. 127 (45), 15824-15832, 2005.

Compounds of formula Iaa can be further used for the preparation of compounds of formula Iad (Scheme 15). Indeed, Formula Iaa, wherein X is S, SO or SO ₂ , where A, X ₁ , R ₁ and R ₂ are as defined above, where Qx is Compounds that are direct bonds or (CH ₂ ) _n , where n is 1, 2 or 3) are prepared under conditions known to those skilled in the art (aqueous basic or acidic conditions; eg, from 20 ° C. to reflux conditions) At the temperature of formula Iac (wherein X is S, SO or SO ₂ ), under lithium hydroxide or sodium hydroxide in an alcohol solvent such as methanol, wherein A, X ₁ , R ₁ and R ₂ is as defined above, where Qx is a direct bond or is hydrolyzed to a compound of (CH ₂ ) _n and n is 1, 2 or 3. obtain. Optionally at a temperature of 20-100 ° C. with a reagent such as sulfur tetrafluoride SF ₄ or Fluoread (4-tert-butyl-2,6-dimethylphenylsulfur trifluoride) in the presence of hydrogen fluoride HF Treatment of a compound of formula Iac results in formula Iad where X is S, SO or SO ₂ , where A, X ₁ , R ₁ and R ₂ are as defined above, where In which Qx is a direct bond or is (CH ₂ ) _n and n is 1, 2 or 3.

Compounds of formula Iaa can also be used in the preparation of compounds of formula Iaf (Scheme 15a).

As shown in Scheme 15a, Formula Iaa wherein X is S, SO or SO ₂ , where A, X ₁ , R ₁ and R ₂ are as defined above, where In which Qx is a direct bond or (CH ₂ ) _n and n is 1, 2 or 3) under conditions known to those skilled in the art (aqueous basic or acidic conditions; Lithium hydroxide or sodium hydroxide in an alcoholic solvent such as methanol at a temperature of 20 ° C. to reflux conditions; or optionally 20 ° C. to a reflux condition of an aqueous sulfuric acid solution in the presence of a co-solvent). Formula Iaf, wherein X is S, SO or SO ₂ , wherein A, X ₁ , R ₁ and R ₂ are as defined above, wherein Qx is a direct bond Or (CH ₂ ) _n and n is 1, 2 or Or 3).

Alternatively, compounds of formula Iaa can be prepared as shown in Schemes 16 and 17. As shown in Scheme 16, the chemical reactions used are the same as those described in Scheme 15, only the substrate of the reaction is different. Thus, the compounds XXIV and / or XXIV-a described above, as described in Scheme 15, wherein X is S, SO or SO ₂ (especially SO ₂ ), where A, R 1 Is as defined above, where Xb ₄ is, for example, a halogen such as chlorine, bromine or iodine (preferably bromine), or an aryl sulfonate or alkyl sulfonate such as trifluoromethanesulfonate. Where R _LG is C ₁ -C ₄ alkyl) and trimethylsilyl-acetonitrile TMSCN is a compound of the formula XXV where X is S, SO or SO ₂ (especially SO ₂ Where A, R 1 is as defined above, wherein R ₅₀ is C ₁ -C ₄ alkyl). These can be reacted with a compound of Formula XXXII as described in Scheme 15 to form Formula XXVI where X is S, SO or SO ₂ (especially SO ₂ ), where Qx , A, R ₁ as defined above, wherein R ₅₀ is C ₁ -C ₄ alkyl). Similarly, compound XXVI can be prepared directly from XXIV and / or XXIV-a by the chemical reaction described in Scheme 15 involving reagent XXXIII. Compounds of formula XXVI are readily hydrolyzed by methods known to those skilled in the art to be of formula XXVII where X is S, SO or SO ₂ (especially SO ₂ ), where Qx, A , R ₁ is as defined above).

The chemical reaction shown in Scheme 17 is described in detail above (see, eg, Scheme 8). This chemical reaction is activated species XXVIIa, where X is S, SO or SO ₂ (especially SO ₂ ), where Qx, A, R ₁ are as defined above, Where LG ₁ is typically chlorine) followed by amide coupling with a compound of formula XIII, or a salt thereof, to obtain a compound of formula XV-a. Those compounds of formula XV-a can then be converted to compounds of formula Iaa by the formal dehydration step described above in Scheme 8. The definitions of all substituents in Scheme 17 are as described above.

（式中、
Ｒ₁、Ｒ₂、Ｒ₃、ＸおよびＡが、上の式Ｉで定義されるとおりであり、ここで、
Ｑが、基

であり、ここで、Ｒ₀₀₀₂がシアノである）
の化合物は、新規であり、特に、本発明に係る式Ｉの化合物の調製のために開発されたものであり、したがって、本発明のさらなる対象である。式Ｉの化合物の置換基の選択および好ましい実施形態は、式ＸＶ−ｉｎｔの化合物にも有効である。 Formula XV-int

(Where
R ₁ , R ₂ , R ₃ , X and A are as defined in Formula I above, where
Q is the group

Where R ₀₀₀₂ is cyano)
These compounds are new and have been developed in particular for the preparation of compounds of the formula I according to the invention and are therefore a further subject of the invention. The choice of substituents and preferred embodiments of compounds of formula I are also valid for compounds of formula XV-int.

Compounds of formula I (wherein Q is substituted C ₃ -cycloalkyl), which forms a subgroup represented by compounds of formula Iae, are obtained from compounds of formula XXVIII by a chemical reaction shown in Scheme 18. Can be prepared.

In Scheme 18, Formula XXVIII, wherein R ₁ , R ₂ , X ₁ and A are as previously defined, wherein X is S, SO or SO ₂ , wherein R ₀₁ Are halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ cyclo-alkyl or phenyl) at ambient temperatures or below, inert compounds such as methylene chloride or ether Treated with diazomethane CH ₂ N ₂ in a solvent in the presence of a catalyst such as Pd (OAc) ₂ or bis (benzonitrile) palladium (II) dichloride, wherein the substituent is defined by formula XXVIII Compound) is formed. Such chemical reactions are described in the literature (for example Org. Biomol. Chem. 2, 2471, 2004, WO 03/064418, or Med. Chem. Letts., 4, 514-516, 2013). See).

（式中、Ａ、Ｒ₁、Ｒ₂、ＸおよびＸ₁が式Ｉに記載されるとおりであり、Ｑが、ハロゲンで二置換されるＣ₃−シクロアルキルであり、ここで、Ｒ₀₂が、ハロゲン、好ましくは、フッ素、塩素または臭素である）
の化合物によって表される。 Another specific example of a compound of formula I is of formula Ib:

Wherein A, R ₁ , R ₂ , X and X ₁ are as described in Formula I and Q is C ₃ -cycloalkyl disubstituted with halogen, wherein R ₀₂ is , Halogen, preferably fluorine, chlorine or bromine)
Represented by the compound

（式中、Ａ、Ｒ₁、Ｒ₂およびＸ₁が式Ｉに記載されるとおりであり、ここで、Ｒ₀₂が、塩素または臭素である）
の化合物は、好ましくは、約０℃〜３０℃の温度において、任意選択的に、ジクロロメタンなどのさらなる溶媒の存在下で、任意選択的に、例えばテトラブチルアンモニウムブロミドまたはトリエチルベンジルアンモニウムクロリドなどの相間移動触媒ＰＴＣの存在下で、濃縮された水酸化ナトリウムまたは水酸化カリウム水溶液の存在下で、例えば、式ＸＸＶＩＩＩ−ａ（式中、Ａ、Ｒ₁、Ｒ₂およびＸ₁が式Ｉに記載されるとおりである）の化合物をクロロホルムＣＨＣｌ₃またはブロモホルムＣＨＢｒ₃（場合により試薬および溶媒として作用する）と反応させることによって調製され得る。このような化学反応は、文献に記載されている（例えばＳｃｉｅｎｃｅ ｏｆ Ｓｙｎｔｈｅｓｉｓ，３４，２４５−２６５，２００６を参照）。あるいは、式Ｉ−ｂ−１（式中、Ａ、Ｒ₁、Ｒ₂およびＸ₁が式Ｉに記載されるとおりであり、ここで、Ｒ₀₂がフッ素である）の化合物は、１００〜２００℃（好ましくは、１５０〜２００℃の範囲）の温度において、ジグリム、テトラヒドロフラン、ジオキサンまたはジメトキシエタンなどの溶媒中で、例えば、式ＸＸＶＩＩＩ−ａ（式中、Ａ、Ｒ₁、Ｒ₂およびＸ₁が式Ｉに記載されるとおりである）の化合物をクロロジフルオロ酢酸ナトリウム（ＣｌＣＦ₂ＣＯ₂Ｎａ）、ブロモジフルオロ酢酸ナトリウム（ＢｒＣＦ₂ＣＯ₂Ｎａ）またはトリフルオロ酢酸ナトリウム（ＣＦ₃ＣＯ₂Ｎａ）などの試薬と反応させることによって調製され得る。このような化学反応は、文献に記載されている（例えばＳｙｎｔｈｅｓｉｓ，２０８０−２０８４，２０１０を参照）。 Formula Ib-1 (a specific subset of compounds Ib where X is S (sulfide))

Wherein A, R ₁ , R ₂ and X ₁ are as described in Formula I, where R ₀₂ is chlorine or bromine
The compound is preferably at a temperature of about 0 ° C. to 30 ° C., optionally in the presence of a further solvent such as dichloromethane, optionally in the interphase such as tetrabutylammonium bromide or triethylbenzylammonium chloride. In the presence of the transfer catalyst PTC, in the presence of concentrated aqueous sodium hydroxide or potassium hydroxide, for example, the formula XXVIII-a (wherein A, R ₁ , R ₂ and X ₁ are described in formula I) Can be prepared by reaction with chloroform CHCl ₃ or bromoform CHBr ₃ (optionally acting as a reagent and solvent). Such chemical reactions are described in the literature (see, for example, Science of Synthesis, 34, 245-265, 2006). Alternatively, a compound of formula Ib-1 (wherein A, R ₁ , R ₂ and X ₁ are as described in formula I where R ₀₂ is fluorine) is from 100 to 200 ° C. (preferably, 150 to 200 range ° C.) at a temperature of, diglyme, tetrahydrofuran, in a solvent such as dioxane or dimethoxyethane, for example, the formula XXVIII-a (wherein, a, R _1, R ₂ and X ₁ Are as described in Formula I) such as sodium chlorodifluoroacetate (ClCF ₂ CO ₂ Na), sodium bromodifluoroacetate (BrCF ₂ CO ₂ Na) or sodium trifluoroacetate (CF ₃ CO ₂ Na) It can be prepared by reacting with the following reagents. Such chemical reactions are described in the literature (see, for example, Synthesis, 2080-2084, 2010).

Using a suitable oxidant, Formula Ib-2 (wherein A, R ₁ , R ₂ and X ₁ are as described in Formula I, wherein R ₀₂ is halogen, preferably , Fluorine, chlorine or bromine, wherein X is SO or SO ₂ , wherein formula Ib-1 wherein A, R ₁ , R ₂ and X ₁ are of formula I In which R ₀₂ is halogen, preferably fluorine, chlorine or bromine, can be carried out under the conditions already described above.

Alternatively, a compound of formula Ib-2 (wherein X is SO or SO ₂ ) can be modified by changing the order of the steps (ie, from XXVIII-a to XXVIII-b by oxidation). run, followed by di-halo cyclopropanation step, (wherein, X is a is SO or SO _{2) I-b-2} by forming a) except, the same chemical reactions as discussed above By inclusion, it can be prepared from a sulfide compound of formula XXVIII-a.

（式中、置換基が、上の式Ｉで定義されるとおりである）
の化合物によって表される。式Ｉａａ−ｐの化合物は、式Ｉ−Ａ（式中、Ｑが、基

であり、ここで、Ｒ₀₀₂₀がシアノであり、Ｑｘが、上に定義されるとおりである）の化合物の特定のサブセットである。 A method according to the invention for preparing compounds of formula I (wherein Q is in position 4 above), as well as explanations for all relevant intermediates (see text, explanations and methods of preparation above) Is optionally modified by changing the order of a series of specific steps and by slightly modifying the reaction conditions in a manner known to those skilled in the art, wherein Q is in the 3-position. The same applies to the preparation of the compounds. In Scheme 19, a compound of formula I (wherein Q is in the 3-position) is a compound of formula IA

Wherein the substituent is as defined in Formula I above.
Represented by the compound A compound of formula Iaa-p has the formula IA where Q is a group

Where R ₀₀₂₀ is cyano and Qx is as defined above).

Such a rearrangement of a compound of formula IA (or Iaa-p) from intermediate II-p (wherein all substituent definitions given above are also valid for the indicated compound). Shown in Scheme 19 for the preparation.

  The reactant can be reacted in the presence of a base. Examples of suitable bases are alkali metal or alkaline earth metal hydroxide, alkali metal or alkaline earth metal hydride, alkali metal or alkaline earth metal amide, alkali metal or alkaline earth metal alkoxide, alkali metal or alkali Earth metal acetate, alkali metal or alkaline earth metal carbonate, alkali metal or alkaline earth metal dialkylamide or alkali metal or alkaline earth metal alkylsilylamide, alkylamide, alkylenediamide, free or N-alkylated saturation Or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxide and carbocyclic amines. Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis (trimethylsilyl) ) Amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N, N-dimethylamine, N, N-diethylaniline, pyridine, 4- (N, N-dimethylamino) pyridine, Quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide and 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU).

  The reactants can be reacted with each other as they are, i.e. without adding a solvent or diluent. In most cases, however, it is advantageous to add inert solvents or diluents or mixtures thereof. If the reaction is carried out in the presence of a base, an excess of base such as triethylamine, pyridine, N-methylmorpholine or N, N-diethylaniline can also serve as a solvent or diluent.

  The reaction is advantageously carried out in a temperature range from about -80 ° C to about + 140 ° C, preferably from about -30 ° C to about + 100 ° C, often in the range from ambient temperature to about + 80 ° C.

  A compound of formula I can be converted to another compound of formula I by substituting one or more substituents of the starting compound of formula I with other substituents according to the invention in a conventional manner. It can be converted in a manner known per se.

  Depending on the choice of suitable reaction conditions and starting materials, for example, in one reaction step it is possible to simply substitute one substituent with another substituent according to the invention, or several substituents Can be substituted with other substituents according to the invention in the same reaction step.

  Salts of compounds of formula I can be prepared in a manner known per se. Thus, for example, acid addition salts of compounds of formula I are obtained by treatment with a suitable acid or suitable ion exchange reagent, and salts with a base are obtained by treatment with a suitable base or suitable ion exchange reagent.

  Salts of compounds of formula I can be prepared, for example, by treatment with a suitable basic compound or a suitable ion exchange reagent, to acid addition salts of the free compounds I and, for example, by treatment with a suitable acid or a suitable ion exchange reagent. Can be converted to salts with bases in a conventional manner.

  The salt of the compound of formula I is insoluble in, for example, an inorganic salt that forms silver chloride, and thus, in a suitable solvent that precipitates from the reaction mixture, for example, an inorganic acid salt such as the hydrochloride salt of an acid sodium salt, barium salt Or converted to other salts, acid addition salts, eg other acid addition salts of the compounds of the formula I in a manner known per se by treatment with a suitable metal salt such as silver salt, for example silver acetate. obtain.

  Depending on the procedure or reaction conditions, compounds of formula I with salt-forming properties are obtained in free form or in salt form.

  Compounds of formula I and optionally tautomers thereof, each appear in free or salt form, depending on the number, absolute and relative configuration of asymmetric carbon atoms appearing in the molecule and / or in the molecule Depending on the arrangement of the non-aromatic double bonds, for example in the form of pure isomers such as enantiomers and / or diastereomers, or enantiomeric mixtures such as racemates, diastereomeric mixtures or racemic May exist as a mixture of isomers, such as a mixture of isomers, in one form of possible isomers or as a mixture thereof; the present invention relates to pure isomers and also to all possible isomer mixtures, Even if the details of the stereochemistry are not specifically described, they should be understood in this sense, both above and below.

  Diastereomeric or racemic mixtures of the compounds of formula I are obtained in free or salt form, depending on which starting materials and procedures are selected, for example by fractional crystallization, distillation and / or chromatography. Based on these physicochemical differences, they can be separated into pure diastereomers or racemates by known methods.

  Enantiomeric mixtures such as racemates obtained in a similar manner can be obtained by known methods, for example by recrystallization from optically active solvents, chromatography in chiral adsorbents, for example acetylcellulose using suitable microorganisms. By high-performance liquid chromatography (HPLC), for example by cleavage with a specific immobilized enzyme via formation of an inclusion compound, using a chiral crown ether in which only one enantiomer is complexed, or by diastereo Conversion to the mer salt, for example, reacts the basic end product racemate with a carboxylic acid such as camphoric acid, tartaric acid or malic acid, or an optically active acid such as sulfonic acid such as camphorsulfonic acid and thus obtained. Diastereomeric mixtures obtained, for example, into fractional crystals based on different solubilities. Separated I, suitable materials, for example by the action of a basic substance, by obtaining a diastereomer desired enantiomer can be released therefrom, it can be resolved into the optical antipodes.

  Pure diastereomers or enantiomers are not only separated according to the invention by separating suitable isomer mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, for example It can also be obtained by carrying out the process according to the invention using starting materials having stereochemical properties.

N-oxides can be prepared by reacting a compound of formula I with a suitable oxidizing agent, such as H ₂ O ₂ / urea adduct, in the presence of an acid anhydride, such as trifluoroacetic anhydride. Such oxidation is described, for example, in J. Org. Med. Chem. , 32 (12), 2561-73, 1989 or WO 00/15615.

  If the individual components have different biological activities, each of the biologically more effective isomers, e.g. enantiomers or diastereomers, or isomer mixtures, e.g. enantiomer mixtures or diastereomeric mixtures, is It is advantageous to separate or synthesize.

  The compounds of formula I and optionally tautomers thereof can also be obtained in free or salt form, respectively, optionally in the form of hydrates, and / or other solvents such as solids Includes solvents that could be used to crystallize the compound present in form.

  The compounds represented in Tables 1-18 below may be prepared according to the methods described above. The examples that follow are intended to illustrate the invention and to show preferred compounds of formula I.

（式中、Ｒａ₁、Ｒ₂、Ｇ₁、Ｇ₂、Ｇ₃、Ｇ₄およびＧ₅が、以下に定義されるとおりである）
の１８の置換基の定義Ｘ．００１〜Ｘ．０１８および表Ｘの化合物のＮ−オキシドを開示する。Ｐｈがフェニル基を表し、シクロ−Ｃ３がシクロプロピル基である。 Table X: This table shows the formula I-1a:

(Wherein Ra ₁ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are as defined below)
Definition of 18 substituents of X. 001-X. 018 and N-oxides of compounds of Table X are disclosed. Ph represents a phenyl group, and cyclo-C3 is a cyclopropyl group.

を有する。 Table 1: This table shows the formula I-1a where Xa ₁ is S and Ra ₁ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table X 18 compounds 1.001 to 1.018 are disclosed. For example, compound number 1.001 has the following structure:

Have

Table 2: This table shows the formula I-1a where Xa ₁ is SO and Ra ₁ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table X 18 compounds 2.001 to 2.018 are disclosed.

Table 3: This table shows the formula I-1a where Xa ₁ is SO ₂ and Ra ₁ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table X 18 compounds 3.001 to 3.018 are disclosed.

（式中、Ｒａ₂、Ｒ₂、Ｇ₁、Ｇ₂、Ｇ₃、Ｇ₄およびＧ₅が、以下に定義されるとおりである）
の１８の置換基の定義Ｙ．００１〜Ｙ．０１８および表Ｙの化合物のＮ−オキシドを開示する。Ｐｈがフェニル基を表し、シクロ−Ｃ₃がシクロプロピル基である。 Table Y: This table shows the formula I-2a:

(Wherein Ra ₂ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are as defined below)
Definition of 18 substituents of Y. 001-Y. 018 and N-oxides of compounds of Table Y are disclosed. Ph represents a phenyl group, a cycloalkyl -C ₃ is a cyclopropyl group.

Table 4: This table shows the formula I-2a where Xa ₂ is S and Ra ₂ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table Y 18 compounds 4.001 to 4.018 are disclosed.

Table 5: This table shows the formula I-2a where Xa ₂ is SO and Ra ₂ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table Y 18 compounds 5.001 to 5.018 are disclosed.

Table 6: This table shows the formula I-2a where Xa ₂ is SO ₂ and Ra ₂ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table Y 18 compounds 6.001 to 6.018 are disclosed.

（式中、Ａ、Ｒａ₃、Ｒ₇およびＱ_Rxが、以下に定義されるとおりである）
の６つの置換基の定義Ｚ．００１〜Ｚ．００６および表Ｚの化合物のＮ−オキシドを開示する。シクロ−Ｃ４がシクロブチル基を表し、シクロ−Ｃ５がシクロペンチル基であり、シクロ−Ｃ６がシクロヘキシル基である。 Table Z: This table shows the formula I-3a:

(Wherein A, Ra ₃ , R ₇ and Q _Rx are as defined below)
Definition of six substituents of Z. 001-Z. 006 and the N-oxides of the compounds of Table Z are disclosed. Cyclo-C4 represents a cyclobutyl group, cyclo-C5 is a cyclopentyl group, and cyclo-C6 is a cyclohexyl group.

Table 7: This table shows six compounds 7 of formula I-3a, where Xa ₃ is S and Ra ₃ , R ₇ , A and Q _Rx are as defined in Table Z .001 to 7.006 are disclosed.

Table 8: This table shows six compounds 8 of formula I-3a, wherein Xa ₃ is SO and Ra ₃ , R ₇ , A and Q _Rx are as defined in Table Z .001 to 8.006 are disclosed.

Table 9: This table shows 6 compounds of formula I-3a, where Xa ₃ is SO ₂ and Ra ₃ , R ₇ , A and Q _Rx are as defined in Table Z 9.001 to 9.006 are disclosed.

（式中、Ｒａ₄、Ｒ₂、Ｇ₁、Ｇ₂、Ｇ₃、Ｇ₄およびＧ₅が、以下に定義されるとおりである）
の１８の置換基の定義Ｕ．００１〜Ｕ．０１８および表Ｕの化合物のＮ−オキシドを開示する。Ｐｈがフェニル基を表し、シクロ−Ｃ₃がシクロプロピル基である。 Table U: This table shows the formula I-4a:

(Wherein Ra ₄ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are as defined below)
Definition of 18 substituents of U. 001-U. N-oxides of the compounds of 018 and Table U are disclosed. Ph represents a phenyl group, a cycloalkyl -C ₃ is a cyclopropyl group.

Table 10: This table shows the formula I-4a where Xa ₄ is S and Ra ₄ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table U 18 compounds of 10.001 to 10.18 are disclosed.

Table 11: This table shows the formula I-4a where Xa ₄ is SO and Ra ₄ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table U 18 compounds 11.001 to 11.018 are disclosed.

Table 12: This table shows the formula I-4a where Xa ₄ is SO ₂ and Ra ₄ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table U 18 compounds 12.001 to 12.018 are disclosed.

（式中、Ｒａ₅、Ｒ₂、Ｇ₁、Ｇ₂、Ｇ₃、Ｇ₄およびＧ₅が、以下に定義されるとおりである）
の１８の置換基の定義Ｖ．００１〜Ｖ．０１８および表Ｖの化合物のＮ−オキシドを開示する。Ｐｈがフェニル基を表し、シクロ−Ｃ３がシクロプロピル基である。 Table V: This table shows the formula I-5a:

(Wherein Ra ₅ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are as defined below)
Definition of 18 Substituents of V. 001-V. N-oxides of the compounds of 018 and Table V are disclosed. Ph represents a phenyl group, and cyclo-C3 is a cyclopropyl group.

表１３：この表は、式Ｉ−５ａ（式中、Ｘａ₅がＳであり、Ｒａ₅、Ｒ₂、Ｇ₁、Ｇ₂、Ｇ₃、Ｇ₄およびＧ₅が表Ｖ中に定義されるとおりである）の１８種の化合物１３．００１〜１３．０１８を開示する。

Table 13: This table shows the formula I-5a where Xa ₅ is S and Ra ₅ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table V 18 compounds of 13.001 to 13.018 are disclosed.

Table 14: This table shows the formula I-5a where Xa ₅ is SO and Ra ₅ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table V 18 compounds 14.001-14.018 are disclosed.

Table 15: This table shows the formula I-5a where Xa ₅ is SO ₂ and Ra ₅ , R ₂ , G ₁ , G ₂ , G ₃ , G ₄ and G ₅ are defined in Table V 18 compounds 15.015-15.018 are disclosed.

（式中、Ａ、Ｒａ₆、Ｒ₈およびＱ_Rxが、以下に定義されるとおりである）
の６つの置換基の定義Ｗ．００１〜Ｗ．００６および表Ｗの化合物のＮ−オキシドを開示する。シクロ−Ｃ４がシクロブチル基を表し、シクロ−Ｃ５がシクロペンチル基であり、シクロ−Ｃ６がシクロヘキシル基である。 Table W: This table shows the formula I-6a:

(Wherein A, Ra ₆ , R ₈ and Q _Rx are as defined below)
Definition of six substituents of 001-W. 006 and the N-oxides of the compounds of Table W are disclosed. Cyclo-C4 represents a cyclobutyl group, cyclo-C5 is a cyclopentyl group, and cyclo-C6 is a cyclohexyl group.

Table 16: This table shows _six compounds 16 of formula I-6a where Xa ₆ is S and Ra ₆ , R ₈ , A and Q _Rx are as defined in Table W .001 to 16.006 are disclosed.

Table 17: This table shows _six compounds 17 of formula I-6a, where Xa ₆ is SO and Ra ₆ , R ₈ , A and Q _Rx are as defined in Table W .001 to 17.006 are disclosed.

Table 18: This table shows _six compounds of formula I-6a where Xa ₆ is SO ₂ and Ra ₆ , R ₈ , A and Q _Rx are as defined in Table W 18.001 to 18.006 are disclosed.

  The compounds of the formula I according to the invention are active ingredients that are prophylactically and / or therapeutically beneficial in the field of pest control even at low application rates, which have a very favorable biocidal spectrum, It is well tolerated by blood species, fish and plants. The active ingredients according to the invention act not only on normally susceptible animal pests such as insects or representatives of the order Acarina, but also on all or individual developmental stages of resistant animal pests . The insecticidal or acaricidal activity of the active ingredient according to the invention is reduced directly, i.e. as soon as some time has elapsed, e.g. as pest destruction occurring during molting or indirectly, e.g. May appear as egg laying and / or hatching rate.

Examples of the above animal pests are:
From the order of the Acarina, for example, Acalitus spp, Aculus spp, Acaricalus spp, Aceria spp, Acarus siro, mma sp. , Genus Argas spp., Boophilus spp., Brevipalpus spp., Bryobia spp, Calipitrimerus spp. Dermatossus gallinae, Dermatophagoides agoides spp), Eotetranichus spp, Eriophys spp., Hemitarsonemus spp, Olympus sp. Orithodoros spp., Polyphagotarsone latus, Panonychus spp., Phylocoptrosa olneus, Phytophymone sp. s spp), Psoroptes spp., Rhipicphalus spp., Rhizoglyhus spp., Sarcoptes spp. Tarsonemus spp.) And Tetranychus spp .;
From the order of the Anoplura, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp.
From the order of the Coleoptera, for example, Agriotes spp., Amphimalon majale, Anomalas orienta sp. (Astylus atomiculatus), Athenius spp, Atomalia linearis, Chaetocnema tibialis, Genus Cerotosp. spp.), Cotinis nitida, Curculio spp., Cyclocephala spp, Dermestes spp. ab, Diabrotica spp. , Epilacuna spp., Eremnus spp., Heteronychus arter, Hypothenemus hamlipei, Lagria lars ham, Lissohoptrus spp., Liogenys spp, Maecolas spis sp .), Myocrous armatus, Oricaephilus spp., Otiorhynchus spp., Phyllophaga sp., P. pylus sp. ), Psylliodes spp., Rhysomatus abutilis, Rhizopertha spp., S. aphididae, sp. (Somaticus spp), Sphenophorus spp, Sternechus subsignatus, Tenebrio spp., Tribolium spg. Tribolium spg.
From the order of the Diptera, for example, Aedes spp., Anopheles spp, Anteregona soccata, Bactrocea oleia, Bio horsius (Bradysia spp), black fly (Calliphora erythrocephala), Ceratitis spp., Chrysomyia spp., Culex spp., Ctereb spp. , Delia spp, Drosophila m lanogaster, Fannia spp., Gastrophilus spp., Geomiza tripuncta, sp. p. .), Liriomyza spp., Lucilia spp., Melanagromyza spp., Musca spp., Oestru spp., Oestru spp. , Oscinella frit, Pegomii hyoscami), Horbia spp., Ragoletis spp, Liberia quadrifaciata (S), Scatella sp. (S), Scatella sp. Tabanus spp., Tania spp. And Tipula spp .;
From the order of the Hemoptera, for example, Acanthocolis scabrator, Acrosternum spp, Adelphocoris lineolatus, Abricota line, thalassina, Blissus spp, Chimex spp., Claviglala tomentosicollis, Creontiades spp, Distantiella theo dia. Kerpus flucatus, Dysdercus spp., Edessa spp, eustus spp., H. urs. ), Horcias nobilellus, Leptocorisa spp., Lygus spp, Margarodes spp, Murganti memtomirotom ), Tobacco insects (Nesidiocoris tenuis), Nezara spp., Nyius simulans, Oebalus insulazo, Piesma psp. Genus (Rhodnius spp.), Sahlbergella singularis, Scaptocoris castanea, Scotinophara spp., Santinopha spp. ), Vatiga ildenns;
Ashirutoshiumu-Pisumu (Acyrthosium pisum), Adarugesu genus (Adalges spp), Agariana-Enshigera (Agalliana ensigera), Agonosena-Tarugionii (Agonoscena targionii), Areurojikusu genus (Aleurodicus spp), Areurokantsusu genus (Aleurocanthus spp), Areurorobusu-Barodenshisu (Aleurolobus barodensis, Aleurothrixus floccusus, Areyrodes brassicae, Amarasca bituttula, Amritos atkinsoni us atkinsoni), Anonydiella spp., Aphididae, Aphis spp., Aspidiotus spp., Acotoracer sera. , Bemisia spp, Brachycaudus spp, Breconcoryne brassicae, Capposylla spp, Carrotella sp. Cavalipa sp. ), Chrysomphalus aonidium, Chrysomphalus dictyospermi, Cicella spp, Cofida spp, Cofapect Coccus hesperidum, Dalbulus maidis, Dialeurodes spp, Diaphorina citri, Diuraphis noxia (Diuris isp) Poasuka genus (Empoasca spp. ), Apple beetle (Eriosoma larigerum), erythroneuura spp., Genus Gascardia spp., Genus spr. ), Hyperomyzus pallidus, Idioscopus cyperalis, Jacobiasca lybica, Laodelfaxum L. corni), Lepidosaphes spp., Poppy aphid (Lopaphis erysimi), Lyogenys maidis (Macrophum spp.), Maphanarph spp. Mepolophium dirhodum, Myndus crudus, Myzus spp., Neoxoptera sp, genus Nepalp. Ooa Buramushi (Nippolachnus piri Mats), Odonasupisu-Rutae (Odonaspis ruthae), Oreguma-Ranigera-presenters (Oregma lanigera Zehnter), bayberry whitefly (Parabemisia myricae), Paratorioza-Kokkereri (Paratrioza cockerelli), Paruratoria genus (Parlatoria spp.), Pemufigusu Genus (Pemphigus spp.), Corn planthopper (Peregrinus maidis), Perkinsiella spp. (Phordon humuli), phylloxera spp (Phloxera spp) spp. ), Pseudaulacaspis spp., Pseudococcus spp., Pseudomoscelis seriatus, Psylla spp., Psylla spp. Quadraspidiiotus spp.), Quesada gigas, Recilia dorsalis, Rhoparosifum spp., Saisettia spde. ) Shitobion genus (Sitobion spp.), Sejirounka (Sogatella furcifera), Supishisuchirusu-Fesuchinusu (Spissistilus festinus), Tarofagasu - Proserpine (Tarophagus Proserpina), Tokisoputera genus (Toxoptera spp), Toriareurodesu genus (Trialeurodes spp), Torijisukasu-Suporobori (Tridiscus sporoboli ), Trionymus spp, Triza erythrae, Unaspis citri, Zygina flamigera, Zyginia y sid. cutellaris);
From the order of the Hymenoptera, for example, Acromymex, Arge spp, Atchia spp., Cephus spp., Diprion spp. (Diplionidae), Giantia bee (Gilpinia polytoma), Hoplocampa spp., Kearis (Lasius spp.), Yeohimeri (Momomori haraonis), Nediprion (p. Invicta (Slenopsis invicta), Solenopsis genus (Solenopsis s . P) and Vespa species (Vespa spp).;
From the order of the Isoptera, for example, Coptothermes spp, Corniternes cumulans, Incitermes spp, Macrotermes spes, Masterm sp. Microtermes spp., Reticulitermes spp .; Solenopsis geminate
From the order of the Lepidoptera, for example, Acrylis spp., Adoxophys spp., Aegeria spp., Agrotis spp., Alabama algae Algae algae Genus (Amylois spp.), Anticalcia gemmatalis, Archhips spp., Argyrestia spp., Argylotaenia spp. Ratricus thuleberiera (Bucculatrix thurb riella, African swim, Cadra cautella, Carposina nipponensis, Chilo spp., Chiristo spia, Choristonia sp. ambiguella), Cnaphalocrossis spp., Cnephasia spp., Cochiris spp., Coleophora spp., Coliophora sp. ila flava), Crambus spp, Crocidomia binnotalis, Cryptophlevia leucotia, Spidalima perspitalis (Cydaliperp) (Diaphania perspecialis), Diatraea spp., Diparopsis castanea, Earias spp., Eldana saccharina (Eldana saccharina) ), Epinotia spp, Estigmene acrea, Etiella zinkkinella, Eucosma spp., Eupoecilia sp. Genus (Euxoa spp.), Feltia jaculiferia, Graphorita spp., Hedia nuiferana, Heliotis spl., Heithis spl. (Herpetogram a spp), the United States white Arctiidae (Hyphantria cunea), Kei Feria Rikoperushisera (Keiferia lycopersicella), sorghum moth (Lasmopalpus lignosellus), Reukoputera-Shitera (Leucoptera scitella), Ritokorechisu genus (Lithocollethis spp.), Hosobahimehamaki (Lobesia botrana), Loxostege bifidalis, Lymantria spp., Lyonetia spp., Malacosoma spp., Mamestra megass (Mamestra megasas) ca sexta), Mythimna spp, Noctua spp, Operoftera spp., Orniodes indica (Ostribe genus). (Pandemis spp.), Pinelis flammea, Papaipema nebris, Peptinophora gossiipela, Coffee leafhopper (Perileucopter pulp) horimaea operculella), cabbage butterfly (Pieris rapae), Pierisu genus (Pieris spp. ), Plutella xylostella, Place spp., Pseudoplusia spp, Rachiplusia nu, Richia albicopa sp., Richia albicopa sp. (Sesamia spp.), Sparganothis spp., Spodoptera spp., Sylepta derogate, Synanthedon spp. Tortrix spp.), Iraqusaginawaba (T Richioplusia ni), tomato absoluta, and Yponomeuta spp .;
From the order of the Mallophaga, for example, Damarinea spp. And Trichodictes spp .;
From the order of the Orthoptera, for example, the cockroach genus (Blatta spp.), The German cockroach genus (Blattella spp.), The genus (Glylottalpa spp.), The genus cockroach (Leucophaea maderae), the genus sp. Hexaductila (Neocurtila hexadactyla), Cockroach spp., Scapteriscus spp, and Schistocerca spp .;
From the order of the Psocoptera, for example, Liposcelis spp .;
From the order of the Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp. And Xenopsilla cheopes;
From the order of the Thysanoptera, for example, Calliotrips phaseoli, Franchiniella spp., Heliotrips spp, Helsintrips sp., Helsintrips sp. Scitotrips aurantii, Soybean thrips (Sericotrips variabilis), Taeniotrips spp., Thrips spp;
From the order of the Thysanura, for example, Lepisma saccharina.

  The active ingredients according to the invention are those mentioned above which occur in plants, in particular useful plants and ornamental plants in agriculture, horticulture and forests, or in organs such as fruits, flowers, leaves, stems, tubers or roots of such plants. It can be used to control, i.e. control or destroy, types of pests, and in some cases even plant organs formed at a later time remain protected from these pests.

  Suitable target crops are in particular grains such as wheat, barley, rye, oats, rice, corn or sorghum; beets such as sugar beets or feed beets; fruits such as apples, pears, plums, peaches, almonds, cherries Or berries, eg berries such as strawberries, raspberries or blackberries, nuclear fruits or soft fruits; legumes such as kidney beans, lentils, peas or soybeans; rapeseed, mustard, poppy, olive, sunflower, palm, Oils and fats crops such as castor, cacao or ground nut; cucurbits such as pumpkin, cucumber or melon; fiber plants such as cotton, flax, hemp or jute; citrus fruits such as orange, lemon, grapefruit or tangerine Fruits; vegetables such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes or peppers; plants of the Lauraceae such as avocado, cinnamon or camphor; and also tobacco, nuts, coffee, eggplant Sugarcane, tea, pepper, grapes, hops, plantains, and latex plants.

  The active ingredients according to the invention are those mentioned above which occur in plants, in particular useful plants and ornamental plants in agriculture, horticulture and forests, or in organs such as fruits, flowers, leaves, stems, tubers or roots of such plants. It can be used to control, i.e. control or destroy, types of pests, and in some cases even plant organs formed at a later time remain protected from these pests.

  Suitable target crops are in particular grains such as wheat, barley, rye, oats, rice, corn or sorghum; beets such as sugar beets or feed beets; fruits such as apples, pears, plums, peaches, almonds, cherries Or berries, eg berries such as strawberries, raspberries or blackberries, nuclear fruits or soft fruits; legumes such as kidney beans, lentils, peas or soybeans; rapeseed, mustard, poppy, olive, sunflower, palm, Oils and fats crops such as castor, cacao or ground nut; cucurbits such as pumpkin, cucumber or melon; fiber plants such as cotton, flax, hemp or jute; citrus fruits such as orange, lemon, grapefruit or tangerine Fruits; vegetables such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes or peppers; plants of the Lauraceae such as avocado, cinnamon or camphor; and also tobacco, nuts, coffee, eggplant Sugarcane, tea, pepper, grapes, hops, plantains and latex plants.

  The compositions and / or methods of the present invention may be used on any ornamental plant and / or vegetable crop, including flowers, shrubs, hardwoods and evergreen trees.

  For example, the present invention may be used with any of the following ornamental plant species: Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capensis. ), Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (Eg, B. elatior, Shikizaki begonia (B) Semperflorens), B. tubereux), Bougainvillea spp., Braccome (Brac) ycome spp.), Brassica spp. (Ornamental plants), Calceolaria spp., Capsicum annuum, Catharanthus roseus, Cannaspur genus Cannaspur. ), Chrysanthhemum spp., Cinearia spp. (C. maritime), Coreopsis spp., Crassula coccinee (Crasula coccinee) , Dahlia spp., Delphinium (Delphi) nium spp.), Dicentra spectabilis, Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia sp. Genbera spp., Gomphrena globosa, Heliotropium spp., Sunflower (Helianthus spp.), Hibiscus spp. ), Hydrangea spp., Hempestes phyllostachya, Impatiens spp. (I. Walleriana), Iresine sp. (Iresines sp.) Lantana (Lanta) camara, Lavatera trimestris, Caenxewata (Leonotis leonurus), Lilium spp., Mesembrianthema spp. , Nemesia spp ), Tagetes spp., Dianthus spp. (Carnation), Canna spp., Oxalis spp., Bellis spp., Pelargonia (um) spp.) (P. peltatum, P. Zonale), Viola spp. (Pansy), Petunia spp., Phlox spp., Plexanthus Genus (Plecanthanthus spp.), Poinsettia spp., Parthenosissus spp. (P. quinquef) olia, ivy (P. tricuspidata), primula spp., ranunculus spp., rhododron spp., rose eu duck, eu agon spp.), Saintpaulia spp., Akigiri (Salvia spp.), Blue fan flower (Scaevola aemola), Schizanthus wisetonensis, Sedum spp., Sedum spp. Saffinia species (Surfinia spp. ), Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp. And other plant beds.

  For example, the present invention can be used with any of the following vegetable species: Allium spp. A. Porrum, A. ascalonicum, leek (A. fistulosum)), chervil (Athriscus cerefolium), celery (Apium graveolius), asparagus (Asparagus officinalis), sugar beet (p. Buls) .) (B. Oleracea, B. Pekinensis, B. rapa), Capsicum annuum, Cicer arietinum, Endive, Cichorum spp. (C. intybus), Endive, Citrus sp. (C. sativus, C. melo), Cucurbita spp. (C. pepo), Western pumpkin (C. maxima), Cyanara spp. ( Artichoke (C. scorimus), Cardon (C. cardunculus), Black ginseng (Daucus carota), Fennel (Foeni) ulum vulgare, hypericum spp., lettuce (Lactuca sativa), tomato (Lycopersicon spp.) (tomato (L. esculentum), tomato (L. lycopersicum), mint sp. (Ocium basilicum), parsley (Peteroselinum crispum), common bean genus (Paseolus spp.) (Brown bean (P. vulgaris), safflower bean (P. coccineus)), pea (Pisum sativus) Rheum rhaponticum), Mannenrou (Ro emarinus spp. ), Achilli spp., Scorzonera hispanica, Solanum melangena, Spinach oleracea, Valerianella spp. .Eriocarpa)) and broad bean (Vicia faba).

  Preferred ornamental plant species include St. Paulia (African violet), Begonia (Degonia), Dahlia (Dahlia), Gerbera (Gerbera), Hydrangea (Verbena), Vera (Rosa), Kalanchoe (Rosa), Genus (Kalanchoe), poinsettia (Poinsettia), Zion (Aster), cornflower (Centaurea), harshagiku (Coreopsis), delphinium (Delphinium), cornflower (Monarda), Phlox (Plox) Rudbeckia), Mannungusa (Sedum), Petunia (Petunia), Violet (Viola), Tulifuneso Impatiens, Geranium, Chrysanthhemum, Ranunculus, Fuchsia, Salvia, Hortensia, Roses, T .Johnsworth), mint, peppers, tomatoes and cucumbers.

  The active ingredients according to the present invention include bean aphids (Aphis craccivora), Diablotica balteata, Heliothis virescens, peaches aphid (Myzus aphid) in cotton, vegetables, corn, rice and soybean crops. It is particularly suitable for controlling moths (Plutella xylostella) and Spodoptera littoralis. The active ingredient according to the present invention is further comprised of the genus Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), and Emposka (preferably in vegetables and vineyards). It is particularly suitable for controlling Leptinotarsa (preferably in potatoes) and Chilo supressalis (preferably in rice).

  In a further aspect, the present invention relates to plant parasitic nematodes (endoparasitic, semi-endoparasitic and ectoparasitic nematodes), in particular root-knot nematodes, foxtail nematodes (Melodigyne hapla), melodyogyne incognita, (Meloidyne javanica), Alenaria root-knot nematode (Meloidyne arenaria) and other meloidoid genus (Meloidone) species; , Soybean cyst cm Heterodera glycines, sugar beet nematode (Heterodera schachtii), clovercyst nematode (Heterodera trifolii), and other Heterodera species; Aphelenchoides species; Sting nematode, Veronolimus longikaudatus and other Belonolaimus species; pine nematode, ph. Bursaphelencus spp .; Ring nematode, Criconema spp., Criconemella spp., Cliconemoides spp., Mesocricone spp. Implanta nematode (Ditylenchus destructor), Namiki nematode (Ditylenchus dipsaci) and other Dityrenchus species; Heliocotylenchus multiincinctus and other Helicotyrenchus species; Hirshmanniella species; Lance nematode, Hoploaimus species; Niseko nematode, Nacobus species; Needle nematode, Longidus L. ngatas) and other Longidorus species; Pin nematode, Pratylenchus species; Lesne netode, Pylenchus nech, Ptylenchus neg Pratylenchus carbitatus, Pratylenchus goodyyi and other Pratylenchus species; Negroglycen (Burrowing nematode), Bananae imilis and other species of Radhorus; Reniform nematode, Rotyrenchus robustus, genus Rotyrens and other species of Rotyrens Species; Stubby Root nematode, Trichodorus primitibus and other Trichodorus species, Paratrichodenus neto; Tylenchorinchus cytononi, Tylenchorinchus dubius, and other Tylenchorinchus species; Citrus nematode D , Plant parasitic nematodes such as Xifinema species; and Subangina spp. ), Hyspoperine spp., Macroposthonia spp., Melinius spp., Punctodella spp., And Quinisulcus sp. It also relates to a method for controlling damage to plants and plant parts by genus nematode species.

  The compounds of the present invention may also have activity against mollusks. Examples of molluscs include, for example, Ampullariidae; Arion (A. atter, A. circcumscriptus, A. hortensis, A. rufus); Bradybaenidae (Bradybaena fruticum); Cepaea (C. hortensis, C. hortensis) ); Ochlodina; Deroceras (D. agrestis, D. Empiricorum ( Empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatas); Euumphalia; (Galba) (G. trunculata); Helicelia (H. itala, H. obvia); Helicidae Helicigona albustorum )); Helicodiscus; Helix (H. aperta); Limax (L. Cineleoni) L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellas); Lymnacea; Milax (M.gagates, M. marginatus, M. sowerbyi); Opeas; Pomacea (P. acatic) )); The genus Vallonia and the Zanitoides.

  The term “crop” is recombinant so that it is possible to synthesize one or more selectively acting toxins as known, for example, derived from toxin-producing bacteria, in particular Bacillus bacteria. It should be understood to include crops transformed by the use of DNA technology.

  Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus popilliae; or delta-endotoxins such as Cry1Ab, Cry1Ac, Cry1F, Cry1Fa, An insecticidal protein from Bacillus thuringiensis, such as Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or a plant insecticidal protein (Vip), such as Vip1, Vip2, Vip3 or Vip3A; , Photolabdas luminescens, Insecticidal proteins of the genus Photorhabdus spp. Such as Xenorhabdus nematophilus or Xenorhabdus spp .; neurotoxins specific to scorpion toxins, arachnid toxins, bee toxins and other toxins Toxins produced by animals; toxins produced by fungi such as Streptomyces toxins, plant lectins such as pea lectin, barley lectin or Yukinohana lectin; agglutinin; trypsin inhibitor, serine protease inhibitor, Proteinase inhibitors such as patatin, cystatin, papain inhibitor; lysine, corn-RIP, abrin, ruffin, saporin or bryo Ribosome inactivating protein (RIP) such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidase, ecdysone inhibitor, steroid metabolic enzymes such as HMG-COA-reductase, sodium channel or calcium Ion channel blockers such as channel blockers, juvenile hormone esterase, diuretic hormone receptor, stilbene synthase, bibenzyl synthase, chitinase and glucanase.

  In the context of the present invention, δ-endotoxin is eg Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or a plant insecticidal protein (Vip), eg Vip1, Vip2, Vip3 or Vip3A, also clearly, Understood by toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by new combinations of different domains of these proteins (see, eg, WO 02/15701). Cleaved toxins such as cleaved Cry1Ab are known. In the case of modified toxins, one or more amino acids of the natural toxin are replaced. In such an amino acid substitution, preferably a non-naturally occurring protease recognition sequence is inserted into the toxin, for example in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into the Cry3A toxin (WO 03/053). No. 018810).

  Examples of such toxins or transgenic plants capable of synthesizing such toxins are described, for example, in EP 0 374 753, WO 93/07278, WO 95/34656. European Patent Application Publication No. 0427529, European Patent Application Publication No. 451878 and International Publication No. 03/052073.

  Methods for the preparation of such transgenic plants are generally known to those skilled in the art and are described, for example, in the above-mentioned publications. CryI deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP 0367474, EP 0401979 and WO 90/13651 It is.

  The toxins contained in the transgenic plants confer resistance to the pests. Such insects are found in the insect taxon, but are particularly common in beetles (Coleoptera), Diptera (Diptera) and moths (Lepidoptera). It is done.

  Transgenic plants that contain one or more genes encoding insecticidal resistance and expressing one or more toxins are known, some of which are commercially available. Examples of such plants include YieldGard® (a corn variety that expresses Cry1Ab toxin); YieldGard Rootworm® (a corn variety that expresses Cry3Bb1 toxin); YieldGard Plus® (Cry1Ab and Cry3Bb1 toxin) Corn varieties); Starlink® (corn varieties expressing Cry9C toxin); Herculex I® (Cry1Fa2 toxin, and the enzyme phosphinotricin N-acetyl to obtain resistance to the herbicide glufosinate ammonium Corn varieties expressing transferase (PAT); NuCOTN 33B® (cotton varieties expressing Cry1Ac toxin); Boll ard I® (cotton varieties expressing Cry1Ac toxin); Bollgard II® (cotton varieties expressing Cry1Ac and Cry2Ab toxins); VipCot® (cotton varieties expressing Vip3A and Cry1Ab toxins) NewLeaf® (potato variety expressing Cry3A toxin); NatureGuard®, Agrisure® GT Advantage (GA21 glyphosate resistant trait), Agurisure® CB Advantage trait (Bt11C Awanome trait) ) And Protecta®.

Further examples of such transgenic crops are as follows:
1. Bt11 corn from Syngenta Seeds SAS (Chemin de l'Hobit 27, F-31 790 St. Sauveur, France), registration number C / FR / 96/05/10. Genetically modified maize conferred resistance to attack by European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated Cry1Ab toxin. Bt11 corn also expresses the enzyme PAT by genetic engineering in order to gain resistance to the herbicide glufosinate ammonium.

2. Bt176 corn from Syngenta Seeds SAS (Chemin de l'Hobit 27, F-31 790 St. Sauveur, France), registration number C / FR / 96/05/10. Genetically modified maize conferred resistance to attack by European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of Cry1Ab toxin. Bt176 maize also expresses the enzyme PAT by genetic engineering in order to gain resistance to the herbicide glufosinate ammonium.

3. MIR604 maize from Syngenta Seeds SAS (Chemin de l'Hobit 27, F-31 790 St. Sauveur, France), registration number C / FR / 96/05/10. Corn made insect resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic corn plants is described in WO 03/018810.

4). Monsanto Europe S. A. MON 863 corn, registration number C / DE / 02/9, manufactured by (270-272 Avenue de Turbanen, B-1150 Brussels, Belgium). MON 863 expresses the Cry3Bb1 toxin and is resistant to certain Coleoptera insects.

5. Monsanto Europe S. A. IPC 531 cotton manufactured by (270-272 Avenue de Turbanen, B-1150 Brussels, Belgium), registration number C / ES / 96/02.

6). 1507 corn from Pioneer Overseas Corporation (Avenue Tesco, 7 B-1160 Brussels, Belgium), registration number C / NL / 00/10. Genetically modified maize for expression of the PAT protein to obtain resistance to the protein Cry1F and the herbicide glufosinate ammonium to obtain resistance to certain Lepidoptera insects.

7). Monsanto Europe S. A. NK603 × MON 810 corn, registration number C / GB / 02 / M3 / 03, manufactured by (270-272 Avenue de Türren, B-1150 Brussels, Belgium). It consists of hybrid corn varieties bred by conventional methods by crossing genetically modified varieties NK603 and MON810. NK603 × MON 810 corn is a protein CP4 EPSPS obtained from Agrobacterium sp. Strain CP4 that confers resistance to the herbicide Roundup® (containing glyphosate), and certain species including European corn borer The Cry1Ab toxin obtained from Bacillus thuringiensis subsp. Kurstaki, which provides resistance to Lepidoptera, is also expressed by genetic recombination.

  Transgenic crops of insect-tolerant plants are also described in BATS (Zentrum fuerheitund Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003, (http://bats.ch).

  The term “crop” refers to an antipathogenic substance having a selective action such as, for example, a so-called “pathogenicity-related protein” (PRP, see, for example, EP 0 392 225). It should be understood to include crops transformed by the use of recombinant DNA technology so that they can be synthesized. Examples of such anti-pathogenic substances and transgenic plants capable of synthesizing such anti-pathogenic substances are described, for example, in EP 0 392 225, WO 95/33818. And from EP 0 353 191 A1. Methods for producing such transgenic plants are generally known to those skilled in the art and are described, for example, in the above-mentioned publications.

  The crops can also be fungi (eg Fusarium, anthrax, or Phytophthora), bacteria (eg Pseudomonas) or viruses (eg potato leaf curl virus, tomato yellow gangrene virus, cucumber mosaic virus). ) Can be modified for improved resistance to pathogens.

  Crops also include crops with improved resistance to nematodes such as soybean cyst nematodes.

  Crops that are resistant to abiotic stress are improved against dryness, high salinity, high temperature, cold, frost, or light radiation, eg, through expression of NF-YB or other proteins known in the art Includes crops that are resistant.

  Anti-pathogenic substances that can be expressed by such transgenic plants include, for example, ion channel blockers such as sodium channel or calcium channel blockers such as viral KP1, KP4 or KP6 toxins; stilbene synthase; bibenzyl Synthase; chitinase; glucanase; so-called “pathogenicity related proteins” (PRP; see, for example, EP 0 392 225); anti-pathogenic substances produced by microorganisms, eg peptide antibiotics or heterocyclics Antibiotics (see eg WO 95/33818) or protein or polypeptide factors involved in plant pathogen defense (so-called “plant disease resistance genes” described in WO 03/000906) Is mentioned.

  Further areas of use of the compositions according to the invention are the protection of stored goods and the storage environment and raw materials (such as wood and textiles), the protection of floor coverings and buildings, and the hygiene field, in particular pests of the type described above. Protection of humans, livestock and productive livestock from

  The present invention also provides methods for controlling pests (such as mosquitoes and other pathogens; see also http://www.who.int/malaria/vector_control/irs/en/). In one embodiment, a method for controlling pests comprises applying the composition of the invention to a target pest, to its habitat, or to a surface or substrate by brushing, roller coating, spraying, coating or dipping. The process of carrying out is included. As an example, IRS (indoor residual spray) application of surfaces such as walls, ceilings or floors is envisaged by the method of the invention. In another embodiment, it is envisaged that such a composition is applied to a substrate such as a nonwoven or fabric material in the form of a net, garment, bedding, curtain and tent (or a form that can be used in their manufacture). ing.

  In one embodiment, a method for controlling such pests comprises a pesticidally effective amount of a composition of the present invention so as to provide the surface or substrate with effective residual pest control activity. Applying the object to the target pest, to its habitat, or to a surface or substrate. Such application may be performed by brush application, roller application, spraying, application or dipping of the pesticidal composition of the present invention. By way of example, IRS application on a surface such as a wall, ceiling or floor is envisaged by the method of the present invention to provide the surface with effective residual pest control activity. In another embodiment, such compositions for pest persistence control in substrates such as fabric materials in the form of nets, clothing, bedding, curtains and tents (or forms that can be used in their manufacture). It is assumed to be applied.

  Substrates comprising nonwovens, fabrics or nets to be treated can be made of natural fibers such as cotton, raffia, jute, flax, sisal, linen or wool, or synthetic fibers such as polyamide, polyester, polypropylene, polyacrylonitrile. . Polyester is particularly preferred. For example, International Publication No. 2008/151984, International Publication No. 2003/034823, US Pat. No. 5,613,072, International Publication No. 2005/64072, International Publication No. 2006/128870, European Patents. No. 1724392, WO2005113886 or WO2007 / 090907.

  A further field of use of the composition according to the invention is in the field of trunk injection / stem treatment of all ornamental trees and all kinds of fruit trees and nuts.

  In the field of stem injection / stem treatment, the compounds according to the invention are particularly suitable for the above-mentioned Lepidoptera and Coleoptera wood-boring insects, as shown in Table A and Particularly suitable for the wood-perforating insects listed in B.

Table A. Examples of economically important exotic wood-piercing insects

Table B. Examples of economically important native wood-piercing insects

  The present invention also includes, for example, beetles, caterpillars, fire ants, ground pears, ground pears, cormorants, mites, velvet, scale insects, mealybugs, ticks, potato beetles, southern chinch bugs and earthworms. It can be used to control any insect pest that may be present in turfgrass. The present invention can be used to control insect pests at various stages of the life cycle, including eggs, larvae, nymphs and adults.

  In particular, the present invention relates to earthworms (Cyclocephala spp. (Eg, masked chafer, C. lurida), Rhizotrogus spp. (Eg, European Rhesus spp.)). R. majalis), Cotinus spp. (Eg, C. nitida), Popilia spp. (Eg, Japan beetle), P. japonica)), Phyllophaga spp. (Eg, May / June beetle), Athenius spp. (E.g., Black turfgrass atenaius, A. spretus), Maladera spp. (E.g., M. castanea) and Tomalus. Genus (Tomarus spp.), Cotton beetle (Margarodes spp.), Kera (towny, southern), and short-cage types; Scapteriscus spp. (Gryllotalpa africana) and leather jacket (European crane fly) fly), crane fly genus (Tipula spp.)) including, may be used to control insects pests lawn grass roots bait.

  The present invention also includes the beetles (Spodoptera frugiperda), and the common armyworm (Pseudaletia unipuncta, etc.), the genus S. Weevil (such as S. venatas verstitus) and S. parvulus, and sod webworms (Crambus spp.) And tropical sod webworms, (Herpetogramma phaeoperalis) Including etc.), it may be used to control grass insect pests living in the straw.

  The present invention also relates to the mite (Eriophys cynodonodisigashirasigashirasigasushisushienshigashi), the tick (Eriophysus cynodonodisigashirasigashigashigashigashigashigashi), the ticks of Bermudagrass (Eryophyces cynodonodishirasigasushienshigashigashigashigashigashigashigashigashigashigashigashigashi). Scale insects (Antonina graminis), two-lined spotted bugs (Propsia bicinta), leafhoppers, leafworms (Ingredients of Noctuidae), and worms Control insect pests that feed on turfgrass leaves Can be used.

  The present invention can also be used to control other pests of turfgrass, such as the red ant (Solenopsis invicta) that creates anthills on the lawn.

  In the field of hygiene, the composition according to the present invention comprises a hard tick, soft tick, scabies mite, tsutsugamushi, fly (fly flies and licking flies), parasitic fly larvae, lice, It is effective against ectoparasites such as lice, lice and fleas.

Examples of such parasites are:
Among the order of the Anoplurida: Haematopinus spp., Linognus spp., Pediculus spp. And Phtilus spp.

  Among the order of the Mallophagida: Trimenopon spp., Tanpon spp., Trinoton spp., Bovicola spp., Wernekiella er ), Lepikentron spp., Damarina spp., Trichodictes spp. And Felicola spp.

  Among the Diptera and its suborders Nematocerina and Brachycerina, for example, Aedes spp., Anopheles spp. Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomia spp., Curicoes spp. spp.), Hybomitra spp., Atylotus spp., Tabanus spp. Haematopota spp., Philippomyia spp., Braula spp., Musca spp., Musca spp., S. spp. (Haematobia spp.), Morelia spp., Fannia spp., Glossina spp., Calliphora spp., Lucpih spr. spp.), Wohlfahrtia spp., Sarcop aga spp.), Oestrus spp., Hypoderma spp., Gastrophilus spp., Hippobosca spp., Lippo spp. .).

  Among the fleas (Siphonaptida), for example, the genus Human flea (Pulex spp.), The genus Ctenocephalides spp., The genus Nenopsylla spp., And the genus Ceratophyllus spp.

  Among the Heteroptera, for example, Chimex spp., Triatoma spp., Rhodnius spp., Panstromylus spp.

  Among the cockroaches (Blattarida), for example, the cockroach (Blatta orientalis), the cockroach (Peripraneta americana), the German cockroach (Blatellagermanica), and the genus Spella (Supella spp.).

  Among the subclasses Tick (Acaria (Acarida)) and Tick (Metastigmata) and Mesostigmata (eg, Argas spp.), Ornithodorus spp., Otobius (tobus) spp.), Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp. ), Rhipicephalus spp., Dermanyssus spp., Raillietia spp., Pneumonysus spp., Sternostoma spp. And Barroa spp.

  Among the order Actinida (Prostigmata) and Acarida (Astigmata), for example, Acarapis spp., Cheyletiella spp. Ornithocheyletia spp., Myobia spp., Psorgatesspp., Demodex spp., Limtropor spp. , Acarus spp., Tyrophagus spp. lyphus spp.), Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp. The genus (Sarcoptes spp.), The genus Notoedres spp., The genus Knemidocoptes spp., The genus Cytodites spp. And the genus Laminosoptes.

  The composition according to the invention is also suitable for protecting against insect infestation in the case of materials such as wood, textiles, plastics, adhesives, glue, paints, paper and cardboard, leather, floor coverings and buildings. is there.

  The composition according to the invention can be used, for example, against the following pests: Hylorupes bajulus, Chlorophorus pilosis, Anobium puncatum, Xenostobium X rufuvillosum), Petilinus specicornis, Dendrobium pertinex, Ernobius mollis, Onibira citrus, Priopitarum ctus africanus, Lyctus pnicolis, Lyctus linearis, Lyctus pylense, Troxoxyn squirrel ), Tryptodendron spec., Apate monachus, Bostrychus capucins, Heterobostrus bruneus, Heterobostristchurus brunerus Beetles such as Sinoxylon spec. And Dinoderus minutus, as well as Syrex juvencus, Urocerus giga, Urocerus gigus, and Urocerus giga s. ) And other insects of Hymenopteran, as well as Carotermes flavicollis, Cryptothermes brevis, Heterotermes indicola, Rhizocium itermes flavipes), Letty Kurite Rumesu-Santonenshisu (Reticulitermes santonensis), Letty Curie Tel female Rushifugusu (Reticulitermes lucifugus), Mukashishiroari (Mastotermes darwiniensis), Nevada giant termite (Zootermopsis nevadensis) and the Formosan subterranean termite (Coptotermes formosanus) termites, and the like, as well as western A stain such as a stain (Lepisma saccharina).

  The compounds according to the invention can be used as pest control agents in unmodified form, but they are generally formulated into compositions in various ways using formulation aids such as carriers, solvents and surface-active substances. And formulated. The formulations can be in various physical forms such as powders, gels, wettable powders, wettable granules, water-dispersible tablets, effervescent pellets, emulsifiable concentrates, microemulsifiable concentrates. ), Oil-in-water emulsion, oil-flowable, aqueous dispersion, oil-based dispersion, suspoemulsion, capsule suspension, emulsifiable granule, soluble liquid, water-soluble concentrate ( Water or a water miscible organic solvent as a carrier), in the form of an impregnated polymer film or for example the Manual on Development and Use of FAO and WHO Specificity Other forms known from ons for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations can be used directly or diluted prior to use. Dilution can be performed using, for example, water, liquid fertilizer, micronutrients, biological organisms, oils or solvents.

  The formulations can be prepared, for example, by mixing the active ingredient with formulation aids, in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredient may also be formulated with other adjuvants such as finely divided solids, mineral oils, plant or animal derived oils, plant or animal derived modified oils, organic solvents, water, surface active substances or combinations thereof. obtain.

  The active ingredient can also be contained in fine microcapsules. Microcapsules contain an active ingredient in a porous carrier. This allows the active ingredient to be released into the environment in a controlled amount (eg sustained release). Microcapsules usually have a diameter of 0.1 to 500 μm. Microcapsules contain the active ingredient in an amount of about 25 to 95% by weight of the capsule weight. The active ingredient can be in the form of a monolithic solid, in the form of microparticles in a solid or liquid dispersion, or in the form of a suitable solution. Encapsulating membranes are for example natural or synthetic rubber, cellulose, styrene / butadiene copolymers, polyacrylonitrile, polyacrylates, polyesters, polyamides, polyureas, polyurethanes or chemically modified polymers and starch xanthate or to those skilled in the art. Other known polymers may be included. Alternatively, fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of the base, but the microcapsules themselves are not encapsulated.

  Formulation aids suitable for the preparation of the compositions according to the invention are known per se. The following can be used as liquid carriers: water, toluene, xylene, petroleum ether, vegetable oil, acetone, methyl ethyl ketone, cyclohexanone, acid anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane. , Cyclohexanol, alkyl ester of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abiate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N, N-dimethylformamide, Dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol Tyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, α-pinene, d-limonene, lactic acid Ethyl, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, γ-butyrolactone, glycerol, glycerol acetate, diacetate glycerol, triacetate glycerol, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, Isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl Luketone, methyl laurate, methyl octoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol , Propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, acetic acid Amyl, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and amyl alcohol Tetrahydrofurfuryl alcohol, hexanol, higher molecular weight alcohols, such as octanol, ethylene glycol, propylene glycol, glycerol, N- methyl-2-pyrrolidone.

  Suitable solid carriers are, for example, talc, titanium dioxide, granite clay, silica, attapulgite clay, diatomaceous earth, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husk, wheat flour, soy flour, pumice, wood flour, ground Walnut shell, lignin and similar materials.

  Many surface-active substances can be advantageously used in both solid and liquid formulations, particularly in formulations that can be diluted with a carrier prior to use. The surface-active substances may be anionic, cationic, nonionic or polymeric, and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surfactants include, for example, salts of alkyl sulfates such as diethanolammonium lauryl sulfate; salts of alkylaryl sulfonates such as calcium dodecylbenzenesulfonate; alkylphenol / alkylene oxide addition products such as nonylphenol ethoxylate; tridecyl Alcohol / alkylene oxide adducts such as alcohol ethoxylates; soaps such as sodium stearate; salts of alkyl naphthalene sulfonates such as sodium dibutyl naphthalene sulfonate; Esters; sorbitol esters such as sorbitol oleate; quaternary amines such as lauryltrimethylammonium chloride, poly Block copolymers of ethylene oxide and propylene oxide; polyethylene glycol esters of fatty acids such as Chi glycol monostearate and mono - and di - salts of alkyl phosphoric acid ester; and further for example McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp. , Ridgewood New Jersey (1981).

  Additional adjuvants that can be used in pesticide formulations include crystallization inhibitors, viscosity modifiers, suspending agents, dyes, antioxidants, foaming agents, light absorbers, mixing aids, antifoaming agents, complexing agents. Agents, neutralizers or pH adjusters and buffers, corrosion inhibitors, fragrances, wetting agents, absorption enhancers, micronutrients, plasticizers, lubricants, lubricants, dispersants, thickeners, antifreeze agents, bactericides Agents, and liquid and solid fertilizers.

The composition according to the invention may comprise additives comprising oils of plant or animal origin, mineral oils, alkyl esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive in the composition according to the invention is generally from 0.01 to 10%, based on the mixture applied. For example, the oil additive can be added to the spray tank at the desired concentration after the spray mixture has been prepared. Preferred oil additives include mineral or plant-derived oils such as rapeseed oil, olive oil or sunflower oil, emulsified vegetable oils, alkyl esters of plant-derived oils such as methyl derivatives, or animal-derived oils such as fish oil or beef tallow. Preferred oil additives are alkyl esters of C _{8 to} C ₂₂ fatty acids, especially methyl derivatives of C _{12 to} C ₁₈ fatty acids, such as methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate, respectively). And methyl oleate). A number of oil derivatives are known from the Compendium of Herbide Adjuvants, 10 ^th Edition, Southern Illinois University, 2010.

  The compositions of the present invention generally comprise from 0.1 to 99% by weight, in particular from 0.1 to 95% by weight of the compound of the present invention and from 1 to 99.9% by weight of formulation aids (which are preferably Contains 0 to 25% by weight of a surface active substance). Commercial products may preferably be formulated as a concentrate, but the end user will usually use a diluted formulation.

  Application rates vary within wide limits and depend on soil properties, method of application, crop plants, pests to be controlled, current climatic conditions, and other factors depending on the method of application, time of application and target crop It depends on. As a general guide, the compounds can be applied at a rate of 1 to 2000 l / ha, in particular 10 to 1000 l / ha.

  A preferred formulation may have the following composition (wt%):

emulsion:
Active ingredient: 1 to 95%, preferably 60 to 90%
Surfactant: 1-30%, preferably 5-20%
Liquid carrier: 1-80%, preferably 1-35%

Dust agent:
Active ingredient: 0.1 to 10%, preferably 0.1 to 5%
Solid carrier: 99.9-90%, preferably 99.9-99%

Suspension concentrate:
Active ingredient: 5 to 75%, preferably 10 to 50%
Water: 94-24%, preferably 88-30%
Surfactant: 1-40%, preferably 2-30%

Wettable powder:
Active ingredient: 0.5 to 90%, preferably 1 to 80%
Surfactant: 0.5-20%, preferably 1-15%
Solid carrier: 5 to 95%, preferably 15 to 90%

Granule:
Active ingredient: 0.1-30%, preferably 0.1-15%
Solid carrier: 99.5-70%, preferably 97-85%

  The following examples further illustrate the invention but do not limit the invention.

  This combination is thoroughly mixed with the adjuvant, and the mixture is thoroughly ground in a suitable mill to obtain a wettable powder, which is diluted with water to give the desired concentration of suspension. Is obtained.

  This combination is thoroughly mixed with the adjuvants, and the mixture is thoroughly ground in a suitable mill to obtain a powder that can be used directly for seed treatment.

  An emulsion of any required dilution that can be used for plant protection is obtained from this concentrate by dilution with water.

  A ready-to-use dusting agent is obtained by mixing in combination with a carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressing of seeds.

  This combination is mixed with an adjuvant, ground and the mixture is wetted with water. The mixture is extruded and then dried in a stream of air.

  This finely divided combination is uniformly applied to kaolin wetted with polyethylene glycol in a mixer. In this way, a coated granule free from dust is obtained.

  This micronized combination is intimately mixed with the adjuvant to obtain a suspension concentrate, from which suspension of any desired dilution ratio is obtained by dilution with water. With such dilution, live plants as well as plant propagation material can be treated and protected from microbial infestation by spraying, pouring or dipping.

  This micronized combination is intimately mixed with the adjuvant to obtain a suspension concentrate, from which suspension of any desired dilution ratio is obtained by dilution with water. With such dilution, live plants as well as plant propagation material can be treated and protected from microbial infestation by spraying, pouring or dipping.

Sustained release capsule suspension 28 parts of this combination are mixed with 2 parts aromatic solvent and 7 parts toluene diisocyanate / polymethylene-polyphenyl isocyanate mixture (8: 1). This mixture is emulsified in a mixture of 1.2 parts polyvinyl alcohol, 0.05 parts defoamer and 51.6 parts water until the desired particle size is obtained. To this emulsion is added a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts water. The mixture is stirred until the polymerization reaction is complete. The resulting capsule suspension is stabilized by adding 0.25 parts thickener and 3 parts dispersant. The capsule suspension formulation contains 28% active ingredient. The intermediate diameter of the capsule is 8-15 μm. The resulting formulation is applied to the seed as an aqueous suspension in a device suitable for the relevant purpose.

  Formulation types include emulsion concentrate (EC), suspension concentrate (SC), suspoemulsion (SE), capsule suspension (CS), hydrating granules (WG), emulsifying granules ( EG), water-in-oil emulsion (EO), oil-in-water emulsion (EW), microemulsion (ME), oil dispersion (OD), oil-miscible flowable agent (OF), oil-miscible liquid (OL), soluble concentration (SL) micro-dispersion suspension (SU), ultra-low volume liquid (UL), technical concentrate (TK), dispersibility Any technically feasible product combined with concentrate (DC), wettable powder (WP), soluble granules (SG) or agriculturally acceptable adjuvants Agents.

Preparation examples:
“Mp” means melting point (° C.). A free radical represents a methyl group. ¹ H NMR measurements are recorded on a Brucker 400 MHz spectrometer and chemical shifts are given in ppm relative to the TMS standard. As indicated, spectra are measured in deuterated solvents. Compounds were characterized using either the following LCMS or GCMS methods. Characteristic LCMS values obtained for each compound were measured values of retention time (“R _t ”, recorded in minutes) and molecular ion (M + H) ⁺ .

LCMS and GCMS methods:
Method 1 (LCMS / MS-API 2000 / Q trap)
API 2000 mass spectrometer (single quadrupole mass spectrometer) manufactured by Applied Biosystems; ionization method: electrospray; polarity: positive ion. Capillary (kV) 5.5, DP (V) 50.00, Inlet Potential (V) 10, Focusing Potential (V) 400, Ion source temperature (° C.) 200, Ion source gas 1 (Psi) 40, ion source gas 2 (Psi) 50, curtain gas (Psi) 40; mass range: 100 to 800 amu; UV wavelength range (nm): 220 to 260; column type: Zorbax Extended C18; column length : 50 mm; inner diameter of column: 4.6 mm; particle size: 5 μm
Instrument Shimadzu Prominence with the following HPLC gradient conditions
(Solvent A: 10 Mm NH ₄ OAc in water and solvent B: acetonitrile)
Flow rate: 1.2 ml / min

Method 2 (UPLC1)
ACQUITY SQD mass spectrometer (single quadrupole mass spectrometer) manufactured by Waters;
Ionization method: electrospray; polarity: positive ion. Capillary (kV) 3.00, cone (V) 40.00, extraction device (V) 3.00, ion source temperature (° C.) 150, desolvation temperature (° C.) 400, cone gas flow (L / hr) 50 Desolvation gas flow (L / hr) 750; Mass range: 100-800 Da; DAD wavelength range (nm): 210-400; Flow rate: 1.5 ml / min; Column type: Resteck; Column length: 30 mm Column inner diameter: 2.1 mm; particle size: 1.8 μm; temperature: 50 ° C.
Method by Waters ACQUITY UPLC with the following HPLC gradient conditions (solvent A: 0.05% formic acid in water and solvent B: acetonitrile)

Method 3:
Electrospray source (polarity: positive or negative ion, capillary: 3.00 kV, cone range: 30-60 V, extraction device: 2.00 V, ion source temperature: 150 ° C., desolvation temperature: 350 ° C., cone gas flow: Waters mass spectrometer (SQD or ZQ single quadrupole mass spectrometer) equipped with 0 L / h, desolvation gas flow: 650 L / h, mass range: 100-900 Da) and Waters Acquity UPLC: binary Spectra were recorded with a pump, heated column compartment and diode array detector. Solvent degasser, binary pump, heated column compartment and diode array detector. Column: Waters UPLC HSS T3, 1.8 μm, 30 × 2.1 mm, temperature: 60 ° C., DAD wavelength range (nm): 210-500, solvent gradient: A = water + 5% MeOH + 0.05% HCOOH, B = Acetonitrile + 0.05% HCOOH; gradient: 0% B for 0 min, 100% A; 100% B for 1.2-1.5 min; flow rate (ml / min) 0.85.

Method 4:
GCMS analysis was performed on a Thermo Electron instrument, where a TRACE GC ULTRA gas chromatograph (Zebron Phenomenex ZB-5ms with 15 m, diameter: 0.25 mm, 0.25 μm column; H ₂ flow rate 1.2 mL / min; injection Device temperature: 250 ° C .; detection device temperature: 220 ° C .; method: starting from 70 ° C., then 25 ° C./min until 320 ° C., holding at 320 ° C. for 2 minutes) by electron ionization (EI) Was coupled to a DSQ mass spectrometer for characterization.

ジクロロメタン（１０ｍｌ）中の５−ブロモ−３−クロロ−ピリジン−２−カルボン酸（１ｇ、４．２２ｍｍｏｌ）の撹拌溶液に塩化オキサリル（１．０ｍｌ、１２．６８ｍｍｏｌ）および触媒量のＮ，Ｎ−ジメチルホルムアミドを０℃で加えた。添加後、反応混合物の温度を周囲温度までゆっくりと上昇させ、撹拌を周囲温度で２時間続けた。反応の完了後、溶媒を減圧下で蒸発させたところ、粗５−ブロモ−３−クロロ−ピリジン−２−カルボニルクロリドが得られた。この粗材料をジクロロメタンに溶解させ、０℃でジクロロメタン中のＮ２−メチル−５−（トリフルオロメチル）ピリジン−２，３−ジアミン（０．８８ｇ、４．６５ｍｍｏｌ）およびトリエチルアミン（０．７１ｍｌ、５．０７ｍｍｏｌ）の溶液に滴下して加えた。反応混合物を周囲温度で１６時間撹拌した。反応の完了後、混合物を水（１００ｍｌ）でクエンチし、ジクロロメタンで抽出した。組み合わされた有機層を塩水（１００ｍｌ）で洗浄し、硫酸ナトリウム上で乾燥させ、濃縮した。残渣をｃｏｍｂｉ ｆｌａｓｈ（ヘキサン中２０〜４０％の酢酸エチルの勾配）によって精製したところ、５−ブロモ−３−クロロ−Ｎ−［２−（メチルアミノ）−５−（トリフルオロメチル）−３−ピリジル］ピリジン−２−カルボキサミドがオフホワイトの固体（１．０ｇ）として得られた。ＬＣＭＳ（方法１）：４０９／４１１／４１３（Ｍ＋Ｈ）⁺；保持時間：３．４５分。 Example P1: Preparation of 2- (5-cyclopropyl-3-ethylsulfanyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (Compound P1):
Step 1: Preparation of 5-bromo-3-chloro-N- [2- (methylamino) -5- (trifluoromethyl) -3-pyridyl] pyridine-2-carboxamide:

To a stirred solution of 5-bromo-3-chloro-pyridine-2-carboxylic acid (1 g, 4.22 mmol) in dichloromethane (10 ml) was added oxalyl chloride (1.0 ml, 12.68 mmol) and a catalytic amount of N, N- Dimethylformamide was added at 0 ° C. After the addition, the temperature of the reaction mixture was slowly raised to ambient temperature and stirring was continued at ambient temperature for 2 hours. After completion of the reaction, the solvent was evaporated under reduced pressure to give crude 5-bromo-3-chloro-pyridine-2-carbonyl chloride. This crude material was dissolved in dichloromethane and N2-methyl-5- (trifluoromethyl) pyridine-2,3-diamine (0.88 g, 4.65 mmol) and triethylamine (0.71 ml, 5 0.07 mmol) was added dropwise. The reaction mixture was stirred at ambient temperature for 16 hours. After completion of the reaction, the mixture was quenched with water (100 ml) and extracted with dichloromethane. The combined organic layers were washed with brine (100 ml), dried over sodium sulfate and concentrated. The residue was purified by combi flash (gradient of 20-40% ethyl acetate in hexane) to give 5-bromo-3-chloro-N- [2- (methylamino) -5- (trifluoromethyl) -3- Pyridyl] pyridine-2-carboxamide was obtained as an off-white solid (1.0 g). LCMS (Method 1): 409/411/413 (M + H) ⁺ ; Retention time: 3.45 minutes.

キシレン（５ｍｌ）中の５−ブロモ−３−クロロ−Ｎ−［２−（メチルアミノ）−５−（トリフルオロメチル）−３−ピリジル］ピリジン−２−カルボキサミド（５００ｍｇ、１．２ｍｍｏｌ）の撹拌溶液にｐ−トルエンスルホン酸（９３０ｍｇ、４．８８ｍｍｏｌ）を加え、混合物を６時間にわたって還流させた。反応をＴＬＣによって監視し、出発材料の最大の転化後、混合物を酢酸エチル（５０ｍｌ）に溶解させ、水（５０ｍｌ）および塩水（５０ｍｌ）で洗浄し、硫酸ナトリウム上で乾燥させ、減圧下で濃縮した。粗化合物をｃｏｍｂｉ−ｆｌａｓｈ（ヘキサン中５〜１５％の酢酸エチルの勾配）によって精製したところ、２−（５−ブロモ−３−クロロ−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジンがオフホワイトの固体（２００ｍｇ）として得られた。ＬＣＭＳ（方法１）：３９１／３９３／３９５（Ｍ＋Ｈ）⁺；保持時間：３．６３分。 Step 2: Preparation of 2- (5-bromo-3-chloro-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine:

Stirring of 5-bromo-3-chloro-N- [2- (methylamino) -5- (trifluoromethyl) -3-pyridyl] pyridine-2-carboxamide (500 mg, 1.2 mmol) in xylene (5 ml) To the solution was added p-toluenesulfonic acid (930 mg, 4.88 mmol) and the mixture was refluxed for 6 hours. The reaction was monitored by TLC and after maximum conversion of the starting material, the mixture was dissolved in ethyl acetate (50 ml), washed with water (50 ml) and brine (50 ml), dried over sodium sulfate and concentrated under reduced pressure. did. The crude compound was purified by combi-flash (gradient of 5-15% ethyl acetate in hexane) to give 2- (5-bromo-3-chloro-2-pyridyl) -3-methyl-6- (trifluoromethyl ) Imidazo [4,5-b] pyridine was obtained as an off-white solid (200 mg). LCMS (Method 1): 391/393/395 (M + H) ⁺ ; Retention time: 3.63 minutes.

トルエン（４０ｍｌ；１５分間にわたってＮ₂で溶液を脱気する）中の２−（５−ブロモ−３−クロロ−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（２ｇ、５．１ｍｍｏｌ）の撹拌溶液にシクロプロピルボロン酸（７９０ｍｇ、９．１９ｍｍｏｌ）、トリシクロヘキシルホスフィン（５７３ｍｇ、２．０４ｍｍｏｌ）、リン酸カリウムＫ₃ＰＯ₄（４．３ｇ、２０．４ｍｍｏｌ）を窒素雰囲気下で加えた。反応混合物を１０分間にわたってＮ₂で再度脱気してから、酢酸パラジウム（ＩＩ）Ｐｄ（ＯＡｃ）₂（５７ｍｇ、０．２５ｍｍｏｌ）および水（３．０ｍｌ）を加えた。添加後、反応混合物の温度を還流条件までゆっくりと上昇させ、撹拌を１６時間続けた。反応の完了後、混合物を酢酸エチル（２５０ｍｌ）で希釈し、水（２５０ｍｌ）および塩水（２５０ｍｌ）で洗浄し、硫酸ナトリウム上で乾燥させ、減圧下で濃縮した。粗化合物をカラムクロマトグラフィー（ヘキサン中１０〜１５％の酢酸エチルの勾配）によって精製したところ、２−（３−クロロ−５−シクロプロピル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジンがオフホワイトの固体（５１０ｍｇ）として得られた。ＬＣＭＳ（方法１）：３５３／３５５（Ｍ＋Ｈ）⁺；保持時間：３．６３分。 Step 3: Preparation of 2- (3-chloro-5-cyclopropyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine:

2- (5-Bromo-3-chloro-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5 in toluene (40 ml; degas the solution with N ₂ over 15 min) -B] To a stirred solution of pyridine (2 g, 5.1 mmol), cyclopropylboronic acid (790 mg, 9.19 mmol), tricyclohexylphosphine (573 mg, 2.04 mmol), potassium phosphate K ₃ PO ₄ (4.3 g, 20.4 mmol) was added under a nitrogen atmosphere. The reaction mixture was degassed again with N ₂ for 10 minutes before adding palladium (II) acetate Pd (OAc) ₂ (57 mg, 0.25 mmol) and water (3.0 ml). After the addition, the temperature of the reaction mixture was slowly raised to reflux conditions and stirring was continued for 16 hours. After completion of the reaction, the mixture was diluted with ethyl acetate (250 ml), washed with water (250 ml) and brine (250 ml), dried over sodium sulfate and concentrated under reduced pressure. The crude compound was purified by column chromatography (gradient of 10-15% ethyl acetate in hexane) to give 2- (3-chloro-5-cyclopropyl-2-pyridyl) -3-methyl-6- (trifluoro Methyl) imidazo [4,5-b] pyridine was obtained as an off-white solid (510 mg). LCMS (Method 1): 353/355 (M + H) ⁺ ; Retention time: 3.63 min.

Ｎ，Ｎ−ジメチルホルムアミド（３ｍｌ）中の２−（３−クロロ−５−シクロプロピル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（３００ｍｇ、０．８５ｍｍｏｌ）の撹拌溶液にナトリウムエタンチオレート（１４３ｍｇ、１．７ｍｍｏｌ）を周囲温度で加えた。添加後、反応混合物の温度を還流するまでゆっくりと上昇させ、撹拌を６時間続けた。反応をＬＣ−ＭＳによっておよび完了後に監視し、混合物を酢酸エチル（２０ｍｌ）で希釈し、水で洗浄し、硫酸ナトリウム上で乾燥させ、減圧下で濃縮した。粗化合物を、ヘキサン中１０％のジエチルエーテルを用いて研和し、ろ過し、乾燥させたところ、２−（５−シクロプロピル−３−エチルスルファニル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（表題化合物Ｐ１）がオフホワイトの固体（９０ｍｇ）として得られた（融点１１９〜１２１℃）。ＬＣＭＳ（方法１）：３７９（Ｍ＋Ｈ）⁺；保持時間：３．７６分。 Step 4: Preparation of 2- (5-cyclopropyl-3-ethylsulfanyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (Compound P1):

2- (3-Chloro-5-cyclopropyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (300 mg) in N, N-dimethylformamide (3 ml) , 0.85 mmol) sodium ethanethiolate (143 mg, 1.7 mmol) was added at ambient temperature. After the addition, the temperature of the reaction mixture was slowly increased to reflux and stirring was continued for 6 hours. The reaction was monitored by LC-MS and after completion and the mixture was diluted with ethyl acetate (20 ml), washed with water, dried over sodium sulfate and concentrated under reduced pressure. The crude compound was triturated with 10% diethyl ether in hexane, filtered and dried to give 2- (5-cyclopropyl-3-ethylsulfanyl-2-pyridyl) -3-methyl-6- (Trifluoromethyl) imidazo [4,5-b] pyridine (title compound P1) was obtained as an off-white solid (90 mg) (mp 119-121 ° C.). LCMS (Method 1): 379 (M + H) ⁺ ; Retention time: 3.76 minutes.

亜鉛Ｚｎ（４．３６ｇ、６７．１ｍｍｏｌ）と、塩化リチウムＬｉＣｌ（２．８５ｇ、６７．１ｍｍｏｌ）との混合物を、１０分間にわたってホットガンを用いて高真空下で加熱し、次に、アルゴン雰囲気下で周囲温度に冷却した。乾燥テトラヒドロフラン（２５ｍｌ）を混合物に加えた後、１，２−ジブロモエチレン（０．２ｍｌ）を加え、次に、混合物をゆっくりと５０℃に加熱した。突然、発熱反応が観察された。懸濁液をアルゴン雰囲気下において５０℃で２０分間撹拌した。トリメチルシリルクロリドＴＭＳ−Ｃｌ（０．０５ｍｌ）および次にヨウ素溶液（０．０５ｍｌ、テトラヒドロフラン中０．５Ｍ）を加えた。反応物を５０℃で３０分間撹拌し、シクロペンチルブロミドを同じ温度で滴下して加えた。反応物を５０℃で１６時間撹拌し、周囲温度に冷却し、撹拌を停止して、全ての懸濁された固体材料を沈殿させた。上澄み溶液を反応に使用した。 Example P2: Preparation of 2- (5-cyclopentyl-3-ethylsulfanyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (Compound P2):
Step 1: Preparation of 2- (3-chloro-5-cyclopentyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine

A mixture of zinc Zn (4.36 g, 67.1 mmol) and lithium chloride LiCl (2.85 g, 67.1 mmol) was heated under high vacuum using a hot gun for 10 minutes and then under an argon atmosphere. At ambient temperature. Dry tetrahydrofuran (25 ml) was added to the mixture followed by 1,2-dibromoethylene (0.2 ml) and then the mixture was slowly heated to 50 ° C. Suddenly an exothermic reaction was observed. The suspension was stirred at 50 ° C. for 20 minutes under an argon atmosphere. Trimethylsilyl chloride TMS-Cl (0.05 ml) and then iodine solution (0.05 ml, 0.5 M in tetrahydrofuran) were added. The reaction was stirred at 50 ° C. for 30 minutes and cyclopentyl bromide was added dropwise at the same temperature. The reaction was stirred at 50 ° C. for 16 hours, cooled to ambient temperature, and stirring was stopped to precipitate all suspended solid material. The supernatant solution was used for the reaction.

2- (5-Bromo-3-chloro-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (700 mg, 1.7 mmol) in dry tetrahydrofuran (10 ml) Of 2-dicyclohexyl-phosphino-2 ′, 6′-dimethoxybiphenyl S-PHOS (74 mg, 0.17 mmol), bis (triphenylphosphine) palladium (II) dichloride Pd (PPh ₃ ) ₂ Cl ₂ (120 mg, 0.17 mmol), cyclopentyl zinc bromide (2.3 ml, 3.4 mmol) were added under an argon atmosphere. The reaction mixture was degassed again with argon for 10 minutes and stirred at ambient temperature for 16 hours. After completion of the reaction, the mixture was quenched with water (50 ml), filtered through celite bed, the residue was washed with ethyl acetate, and the aqueous layer was extracted with ethyl acetate (3 × 10 ml). The combined organic layers were washed with brine (10 ml), dried over sodium sulfate and concentrated under reduced pressure. The crude compound was purified by column chromatography (gradient of 10-15% ethyl acetate in dichloromethane) to give the desired compound as an orange sticky solid. This material was washed with diethyl ether (0.5 ml) and n-pentane (5 ml), filtered and dried to give the desired 2- (3-chloro-5-cyclopentyl-2-pyridyl) -3-methyl. -6- (Trifluoromethyl) imidazo [4,5-b] pyridine was obtained as a pale yellow solid (400 mg) (mp 112-114 ° C). LCMS (Method 1): 381/383 (M + H) ⁺ ; Retention time: 4.06 minutes.

Ｎ，Ｎ−ジメチルホルムアミド（３ｍｌ）中の２−（３−クロロ−５−シクロペンチル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（３００ｍｇ、０．７９ｍｍｏｌ）の撹拌溶液にナトリウムエタンチオレート（１３２ｍｇ、１．６ｍｍｏｌ）を周囲温度で加えた。添加後、反応の温度を９０℃までゆっくりと上昇させ、撹拌を３時間続けた。反応をＬＣ−ＭＳによっておよび反応の完了後に監視し、混合物を酢酸エチル（２０ｍｌ）で希釈し、水で洗浄し、硫酸ナトリウム上で乾燥させ、減圧下で濃縮した。粗生成物を、シリカゲルを用いたカラムクロマトグラフィー（ヘキサン中１５％の酢酸エチルの勾配）によって精製したところ、２−（５−シクロペンチル−３−エチルスルファニル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（表題化合物Ｐ２）がオフホワイトの固体（２５０ｍｇ）として得られた。ＬＣＭＳ（方法１）：４０７（Ｍ＋Ｈ）⁺；保持時間：４．２８分。 Step 2: Preparation of 2- (5-cyclopentyl-3-ethylsulfanyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (Compound P2):

2- (3-Chloro-5-cyclopentyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (300 mg, N, N-dimethylformamide (3 ml) To a stirred solution of 0.79 mmol) sodium ethanethiolate (132 mg, 1.6 mmol) was added at ambient temperature. After the addition, the temperature of the reaction was slowly raised to 90 ° C. and stirring was continued for 3 hours. The reaction was monitored by LC-MS and after completion of the reaction, the mixture was diluted with ethyl acetate (20 ml), washed with water, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (15% ethyl acetate in hexane gradient) to give 2- (5-cyclopentyl-3-ethylsulfanyl-2-pyridyl) -3-methyl-6. -(Trifluoromethyl) imidazo [4,5-b] pyridine (title compound P2) was obtained as an off-white solid (250 mg). LCMS (Method 1): 407 (M + H) ⁺ ; Retention time: 4.28 minutes.

乾燥テトラヒドロフラン（１０ｍｌ）中の２−（５−ブロモ−３−クロロ−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（１ｇ、２．５ｍｍｏｌ）の撹拌された脱気溶液に［１，１’−ビス（ジフェニルホスフィノ）フェロセン］ジクロロパラジウム（ＩＩ）Ｐｄ（ｄｐｐｆ）Ｃｌ₂（１８３ｍｇ、０．２５ｍｍｏｌ）およびシクロヘキシル亜鉛ブロミド（１０．２ｍｌ、５．１ｍｍｏｌ、テトラヒドロフラン中０．５Ｍ）をアルゴン雰囲気下で加えた。反応混合物を１０分間にわたってアルゴンで再度脱気した。反応混合物の温度を７０℃までゆっくりと上昇させ、撹拌を１６時間続けた。反応をＴＬＣによっておよび反応の完了後に監視し、混合物を水（５０ｍｌ）でクエンチし、セライト床に通してろ過し、残渣を酢酸エチルで洗浄した。水層を酢酸エチル（３×１０ｍｌ）で抽出し、組み合わされた有機層を塩水（１０ｍｌ）で洗浄し、硫酸ナトリウム上で乾燥させ、減圧下で濃縮した。粗化合物をカラムクロマトグラフィー（ジクロロメタン中１０〜１５％の酢酸エチルの勾配）によって精製したところ、所望の化合物がオレンジ色の粘着性の固体として得られた。この材料をジエチルエーテル（０．５ｍｌ）で洗浄したところ、所望の生成物２−（３−クロロ−５−シクロヘキシル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジンが淡黄色の固体（２５０ｍｇ）として得られた（融点１４４〜１４６℃）。ＬＣＭＳ（方法２）：３９５／３９７（Ｍ＋Ｈ）⁺；保持時間：１．８６分。 Example P3: Preparation of 2- (5-cyclohexyl-3-ethylsulfanyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (Compound P3):
Step 1: Preparation of 2- (3-chloro-5-cyclohexyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine

2- (5-Bromo-3-chloro-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (1 g, 2.5 mmol) in dry tetrahydrofuran (10 ml) Of [1,1′-bis (diphenylphosphino) ferrocene] dichloropalladium (II) Pd (dppf) Cl ₂ (183 mg, 0.25 mmol) and cyclohexylzinc bromide (10.2 ml, 5 0.1 mmol, 0.5 M in tetrahydrofuran) was added under an argon atmosphere. The reaction mixture was degassed again with argon for 10 minutes. The temperature of the reaction mixture was slowly raised to 70 ° C. and stirring was continued for 16 hours. The reaction was monitored by TLC and after completion of the reaction, the mixture was quenched with water (50 ml), filtered through a celite bed and the residue washed with ethyl acetate. The aqueous layer was extracted with ethyl acetate (3 × 10 ml) and the combined organic layers were washed with brine (10 ml), dried over sodium sulfate and concentrated under reduced pressure. The crude compound was purified by column chromatography (gradient of 10-15% ethyl acetate in dichloromethane) to give the desired compound as an orange sticky solid. This material was washed with diethyl ether (0.5 ml) to give the desired product 2- (3-chloro-5-cyclohexyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4 5-b] pyridine was obtained as a pale yellow solid (250 mg) (mp. 144-146 ° C.). LCMS (Method 2): 395/397 (M + H) ⁺ ; Retention time: 1.86 min.

Ｎ，Ｎ−ジメチルホルムアミド（３ｍｌ）中の２−（３−クロロ−５−シクロヘキシル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（３００ｍｇ、０．７６ｍｍｏｌ）の撹拌溶液にナトリウムエタンチオレート（１２８ｍｇ、１．５ｍｍｏｌ）を周囲温度で加えた。添加後、反応混合物の温度を９０℃までゆっくりと上昇させ、撹拌を３時間続けた。反応をＬＣ−ＭＳによっておよび反応の完了後に監視し、混合物を酢酸エチル（２０ｍｌ）で希釈し、水で洗浄し、硫酸ナトリウム上で乾燥させ、減圧下で濃縮した。粗化合物を、シリカゲルを用いたカラムクロマトグラフィー（ヘキサン中１５％の酢酸エチルの勾配）によって精製したところ、所望の生成物２−（５−シクロヘキシル−３−エチルスルファニル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（表題化合物Ｐ３）がオフホワイトの固体（２２０ｍｇ）として得られた（融点１４８〜１５０℃）。ＬＣＭＳ（方法１）：４２１（Ｍ＋Ｈ）⁺；保持時間：４．５２分。 Step 2: Preparation of 2- (5-cyclohexyl-3-ethylsulfanyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (Compound P3)

2- (3-Chloro-5-cyclohexyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (300 mg, N, N-dimethylformamide (3 ml) To a stirred solution of 0.76 mmol) sodium ethanethiolate (128 mg, 1.5 mmol) was added at ambient temperature. After the addition, the temperature of the reaction mixture was slowly raised to 90 ° C. and stirring was continued for 3 hours. The reaction was monitored by LC-MS and after completion of the reaction, the mixture was diluted with ethyl acetate (20 ml), washed with water, dried over sodium sulfate and concentrated under reduced pressure. The crude compound was purified by column chromatography on silica gel (15% ethyl acetate in hexanes gradient) to give the desired product 2- (5-cyclohexyl-3-ethylsulfanyl-2-pyridyl) -3- Methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (title compound P3) was obtained as an off-white solid (220 mg) (mp 148-150 ° C.). LCMS (Method 1): 421 (M + H) ⁺ ; Retention time: 4.52 minutes.

ジクロロメタン（２ｍｌ）中の２−（５−シクロプロピル−３−エチルスルファニル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（１００ｍｇ、０．２６ｍｍｏｌ）の撹拌溶液にメタ−クロロ−ペルオキシ安息香酸（１２８ｍｇ、ｍ−ＣＰＢＡ、約７７％、０．５７ｍｍｏｌ）を０℃で加えた。添加後、反応混合物の温度を周囲温度にゆっくりと上昇させ、撹拌を２時間続けた。反応の完了後、混合物をジクロロメタン（５０ｍｌ）で希釈し、飽和チオ亜硫酸ナトリウム水溶液（１００ｍｌ）および飽和炭酸水素ナトリウム水溶液（１００ｍｌ）で洗浄し、硫酸ナトリウム上で乾燥させ、減圧下で濃縮した。粗化合物をカラムクロマトグラフィー（ヘキサン中２０〜２５％の酢酸エチルの勾配）によって精製したところ、２−（５−シクロプロピル−３−エチルスルホニル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（表題化合物Ｐ４）が粘着性の固体（４０ｍｇ）として得られた。ＬＣＭＳ（方法１）：４１１（Ｍ＋Ｈ）⁺；保持時間：３．４７分。 Example P4: Preparation of 2- (5-cyclopropyl-3-ethylsulfonyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (Compound P4):

2- (5-Cyclopropyl-3-ethylsulfanyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (100 mg, 0.26 mmol) in dichloromethane (2 ml) ) Was added meta-chloro-peroxybenzoic acid (128 mg, m-CPBA, about 77%, 0.57 mmol) at 0 ° C. After the addition, the temperature of the reaction mixture was slowly raised to ambient temperature and stirring was continued for 2 hours. After completion of the reaction, the mixture was diluted with dichloromethane (50 ml), washed with saturated aqueous sodium thiosulfite solution (100 ml) and saturated aqueous sodium bicarbonate solution (100 ml), dried over sodium sulfate and concentrated under reduced pressure. The crude compound was purified by column chromatography (gradient of 20-25% ethyl acetate in hexanes) to give 2- (5-cyclopropyl-3-ethylsulfonyl-2-pyridyl) -3-methyl-6- (tri Fluoromethyl) imidazo [4,5-b] pyridine (title compound P4) was obtained as a sticky solid (40 mg). LCMS (Method 1): 411 (M + H) ⁺ ; Retention time: 3.47 minutes.

窒素雰囲気下において、乾燥Ｎ，Ｎ−ジメチルホルムアミド（１５ｍｌ）中の５−ブロモ−３−フルオロ−ピリジン−２−カルボニトリル（１．００５ｇ、５．００ｍｍｏｌ）の溶液を−５０℃に冷却し、これに乾燥Ｎ，Ｎ−ジメチルホルムアミド（５ｍｌ）中のナトリウムエタンチオレート（０．４２９ｇ、５．１０ｍｍｏｌ）の新たに調製された溶液を滴下して加えた。−５０℃で３０分間撹拌した後、冷却浴を除去し、混合物を周囲温度に温めた。水および塩水を加え、水性混合物を酢酸エチルで抽出した。分離後、有機層を塩水で２回洗浄し、硫酸ナトリウム上で乾燥させ、濃縮した。粗生成物をフラッシュカラムクロマトグラフィー（ヘプタン中０〜４０％の酢酸エチルの勾配）によってシリカ上で精製したところ、表題化合物（０．９３ｇ）が固体として得られた。ＧＣＭＳ（方法４）：２４２／２４４（Ｍ）⁺、保持時間６．３３分。¹Ｈ−ＮＭＲ（ＣＤＣｌ₃、ｐｐｍ）１．４１（３Ｈ）、３．０６（２Ｈ）、７．８２（１Ｈ）、８．４９（１Ｈ）． Example P5: 1- [5-ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl] -3-pyridyl] cyclopropanecarbonitrile ( Preparation step 1 of compound P9) 1: Preparation of 5-bromo-3-ethylsulfanyl-pyridine-2-carbonitrile

Under a nitrogen atmosphere, a solution of 5-bromo-3-fluoro-pyridine-2-carbonitrile (1.005 g, 5.00 mmol) in dry N, N-dimethylformamide (15 ml) was cooled to −50 ° C., To this was added dropwise a freshly prepared solution of sodium ethanethiolate (0.429 g, 5.10 mmol) in dry N, N-dimethylformamide (5 ml). After stirring at −50 ° C. for 30 minutes, the cooling bath was removed and the mixture was allowed to warm to ambient temperature. Water and brine were added and the aqueous mixture was extracted with ethyl acetate. After separation, the organic layer was washed twice with brine, dried over sodium sulfate and concentrated. The crude product was purified on silica by flash column chromatography (gradient of 0-40% ethyl acetate in heptane) to give the title compound (0.93 g) as a solid. GCMS (Method 4): 242/244 (M) ⁺ , retention time 6.33 minutes. ¹ H-NMR (CDCl ₃ , ppm) 1.41 (3H), 3.06 (2H), 7.82 (1H), 8.49 (1H).

Alternative preparation method: A solution of 5-bromo-3-nitro-pyridine-2-carbonitrile (45.35 g, 199 mmol) in dry N, N-dimethylformamide (500 ml) under a nitrogen atmosphere at −50 ° C. To this was added dropwise a freshly prepared solution of sodium ethanethiolate (17.4 g, 207 mmol) in dry N, N-dimethylformamide (200 ml) (not a completely clear solution). ). After complete addition, stirring was continued at −50 ° C. for 30 minutes. Water and brine were added and the cooling bath was removed. The aqueous mixture was extracted with ethyl acetate. After separation, the aqueous layer was extracted once more with ethyl acetate. The combined organic layers were washed twice with brine, dried over sodium sulfate and concentrated. The crude product was purified on silica by flash column chromatography (gradient of 0-25% ethyl acetate in heptane) to give the title compound (33.9 g) as a solid. LCMS (Method 1): 243/245 (M + H) ⁺ ; Retention time: 0.95 min.

８００ｍｌの塩化水素水溶液ＨＣｌ３２％中の５−ブロモ−３−エチルスルファニル−ピリジン−２−カルボニトリル（４３ｇ、１７０ｍｍｏｌ、１．０当量）の溶液を一晩にわたり６０℃に加熱した。ジオキサン（１００ｍｌ）を加え、混合物を６０℃で４８時間さらに撹拌した。反応混合物を０〜５℃に冷却し、ｐＨ１１になるまで水酸化ナトリウム水溶液（ＮａＯＨ３０％）で処理し、２ｘ２００ｍｌのｔｅｒｔ−ブチルメチルエーテルで洗浄した。水相をｐＨ４に戻るようにＨＣｌ１０％で酸性化し、得られた固体をろ過し、水で洗浄し、減圧下で乾燥させた。ＬＣＭＳ（方法１）：２６２、２６４（Ｍ＋Ｈ）⁺；保持時間：０．７７分。¹Ｈ ＮＭＲ（４００ＭＨｚ、ＣＤＣｌ₃）δ ｐｐｍ：８．５０（ｓ，１Ｈ）；８．０６（ｓ，１Ｈ）；３．０３（ｑ，２Ｈ）；１．２４（ｔ，３Ｈ）． Step 2: Preparation of 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylic acid

A solution of 5-bromo-3-ethylsulfanyl-pyridine-2-carbonitrile (43 g, 170 mmol, 1.0 equiv) in 800 ml of aqueous hydrogen chloride HCl 32% was heated to 60 ° C. overnight. Dioxane (100 ml) was added and the mixture was further stirred at 60 ° C. for 48 hours. The reaction mixture was cooled to 0-5 ° C., treated with aqueous sodium hydroxide (NaOH 30%) until pH 11 and washed with 2 × 200 ml tert-butyl methyl ether. The aqueous phase was acidified with HCl 10% to return to pH 4 and the resulting solid was filtered, washed with water and dried under reduced pressure. LCMS (Method 1): 262, 264 (M + H) ⁺ ; Retention time: 0.77 minutes. ¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 8.50 (s, 1H); 8.06 (s, 1H); 3.03 (q, 2H); 1.24 (t, 3H).

メタノール（３５０ｍｌ）中の５−ブロモ−３−エチルスルファニル−ピリジン−２−カルボン酸（１５．０ｇ、５７．２３ｍｍｏｌ）の懸濁液に硫酸（０．５ｍｌ）を加え、混合物を一晩にわたり還流状態で撹拌した。冷却した後、溶液を減圧下で濃縮した。残渣をジエチルエーテル（２００ｍｌ）で研和し、懸濁液をろ過し、固体を冷ジエチルエーテルで洗浄し、減圧下で乾燥させたところ、メチル５−ブロモ−３−エチルスルファニル−ピリジン−２−カルボキシレート（１３．９ｇ）が固体として得られた（融点７２〜７４℃）。ＬＣＭＳ（方法１）：２７６／２７８（Ｍ＋Ｈ）⁺、保持時間０．９８分。¹Ｈ−ＮＭＲ（ＣＤＣｌ₃、ｐｐｍ）１．４２（３Ｈ）、２．９４（２Ｈ）、４．００（３Ｈ）、７．７８（１Ｈ）、８．４６（１Ｈ）． Step 3: Preparation of methyl 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylate

To a suspension of 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylic acid (15.0 g, 57.23 mmol) in methanol (350 ml) was added sulfuric acid (0.5 ml) and the mixture was refluxed overnight. Stir in the state. After cooling, the solution was concentrated under reduced pressure. The residue was triturated with diethyl ether (200 ml), the suspension was filtered and the solid was washed with cold diethyl ether and dried under reduced pressure to give methyl 5-bromo-3-ethylsulfanyl-pyridine-2- Carboxylate (13.9 g) was obtained as a solid (melting point 72-74 ° C.). LCMS (Method 1): 276/278 (M + H) ⁺ , retention time 0.98 minutes. ¹ H-NMR (CDCl ₃ , ppm) 1.42 (3H), 2.94 (2H), 4.00 (3H), 7.78 (1H), 8.46 (1H).

メチル５−ブロモ−３−エチルスルファニル−ピリジン−２−カルボキシレート（２４．４ｇ、８８．４ｍｍｏｌ）をジクロロメタン（２５０ｍＬ）中で懸濁させ、０℃に冷却し、ｍＣＰＢＡ（３７．６ｇ、１８５．７ｍｍｏｌ）で少しずつ処理した。混合物を周囲温度で１８時間撹拌した。混合物を水およびジクロロメタンで希釈し、水相をジクロロメタンで（２回）逆抽出し、組み合わされた有機相をＮａ₂Ｓ₂Ｏ₄で洗浄し、Ｎａ₂ＳＯ₄上で乾燥させた。溶媒の部分的な濃縮により、固体（所望の表題化合物）が得られ、それをろ過した。ろ液を蒸発乾固させ、それをシリカ上でのクロマトグラフィーによって精製したところ、さらなる純粋な表題化合物が白色の固体として得られた。ＬＣＭＳ（方法３）：３０８／３１０（Ｍ＋Ｈ）⁺；保持時間：０．７６分。¹Ｈ ＮＭＲ（ｄ⁶−ＤＭＳＯ、４００ＭＨｚ）：９．０８（ｄ，Ｊ＝２．４Ｈｚ、１Ｈ）、８．５８（ｄ，Ｊ＝２．４Ｈｚ、１Ｈ）、３．８７（ｓ，３Ｈ）、３．５２（ｑ，Ｊ＝７．８Ｈｚ、２Ｈ）、１．１８（ｔ，Ｊ＝７．８Ｈｚ、３Ｈ）． Step 4: Preparation of methyl 5-bromo-3-ethylsulfonyl-pyridine-2-carboxylate

Methyl 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylate (24.4 g, 88.4 mmol) was suspended in dichloromethane (250 mL), cooled to 0 ° C., and mCPBA (37.6 g, 185. 7 mmol). The mixture was stirred at ambient temperature for 18 hours. The mixture was diluted with water and dichloromethane, the aqueous phase was back extracted with dichloromethane (twice) and the combined organic phases were washed with Na ₂ S ₂ O ₄ and dried over Na ₂ SO ₄ . Partial concentration of the solvent gave a solid (the desired title compound) that was filtered. The filtrate was evaporated to dryness and it was purified by chromatography on silica to give more pure title compound as a white solid. LCMS (Method 3): 308/310 (M + H) ⁺ ; Retention time: 0.76 minutes. ¹ H NMR (d ⁶ -DMSO, 400 MHz): 9.08 (d, J = 2.4 Hz, 1H), 8.58 (d, J = 2.4 Hz, 1H), 3.87 (s, 3H) 3.52 (q, J = 7.8 Hz, 2H), 1.18 (t, J = 7.8 Hz, 3H).

ＤＭＦ（１３．０ｍＬ）中のメチル５−ブロモ−３−エチルスルホニル−ピリジン−２−カルボキシレート、（２．００ｇ、６．４９ｍｍｏｌ）の溶液をアルゴン下において、ＴＭＳ−アセトニトリル（２．２５ｇ、２．７１ｍＬ、１９．５ｍｍｏｌ）、ジフルオロ亜鉛（０．４０３ｇ、３．８９ｍｍｏｌ）、キサントホス（０．１５３ｇ、０．２６０ｍｍｏｌ）およびＰｄ₂（ｄｂａ）₃（０．１１９ｇ、０．１３０ｍｍｏｌ）で処理した。得られた混合物を１００℃で５時間撹拌した。この後のＬＣＭＳにより、さらなる反応の進行は示されなかった。混合物を冷却し、ＥｔＯＡｃで希釈し、ｈｙｆｌｏ上でろ過した。ろ液を水／ＮＨ₄Ｃｌ、塩水で洗浄し、Ｎａ₂ＳＯ₄上で乾燥させ、ろ過し、減圧下で濃縮した。粗生成物を、４０ｇのカラムおよびシクロヘキサン＋０〜５０％の酢酸エチルの勾配を用いたｃｏｍｂｉフラッシュクロマトグラフィーによって精製した。これにより、表題化合物が黄色の油として得られた。ＬＣＭＳ（方法３）：２６９（Ｍ＋Ｈ）⁺；保持時間：０．５８分。¹Ｈ ＮＭＲ（４００ＭＨｚ、ＣＤＣｌ₃）δ ｐｐｍ：１．３８（ｔ，Ｊ＝７．５Ｈｚ、３Ｈ）、３．５８（ｑ，Ｊ＝７．５Ｈｚ、２Ｈ）、３．９５（ｓ，２Ｈ）、４．０６（ｓ，３Ｈ）、８．３７（ｄ，Ｊ＝２．２０Ｈｚ、１Ｈ）、８．８６（ｄ，Ｊ＝２．２０Ｈｚ、１Ｈ）． Step 5: Preparation of methyl 5- (cyanomethyl) -3-ethylsulfonyl-pyridine-2-carboxylate

A solution of methyl 5-bromo-3-ethylsulfonyl-pyridine-2-carboxylate, (2.00 g, 6.49 mmol) in DMF (13.0 mL) under TMS-acetonitrile (2.25 g, 2 .71 mL, 19.5 mmol), difluorozinc (0.403 g, 3.89 mmol), xanthophos (0.153 g, 0.260 mmol) and Pd ₂ (dba) ₃ (0.119 g, 0.130 mmol). The resulting mixture was stirred at 100 ° C. for 5 hours. Subsequent LCMS showed no further reaction progress. The mixture was cooled, diluted with EtOAc and filtered over hyflo. The filtrate was washed with water / NH ₄ Cl, brine, dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude product was purified by combi flash chromatography using a 40 g column and a gradient of cyclohexane + 0-50% ethyl acetate. This gave the title compound as a yellow oil. LCMS (Method 3): 269 (M + H) ⁺ ; Retention time: 0.58 min. ¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 1.38 (t, J = 7.5 Hz, 3H), 3.58 (q, J = 7.5 Hz, 2H), 3.95 (s, 2H) 4.06 (s, 3H), 8.37 (d, J = 2.20 Hz, 1H), 8.86 (d, J = 2.20 Hz, 1H).

メチル５−（シアノメチル）−３−エチルスルホニル−ピリジン−２−カルボキシレート（０．６３ｇ、２．３ｍｍｏｌ）をアセトニトリル（１９ｍＬ）に溶解させ、炭酸セシウム（２．３ｇ、７．０ｍｍｏｌ）を無色の溶液に加えた（溶液が暗色化した）後、１，２−ジブロモエタン（０．９０ｇ、０．４１ｍＬ、４．７ｍｍｏｌ）を加えた。褐色の溶液を８０℃の浴温度で撹拌した。ＬＣ／ＭＳにより、１．５時間後にＲｔ＝０．７３分で所望の質量が検出された。反応混合物を減圧下で濃縮し、ＥｔＯＡｃおよび水で希釈した。有機層を分離し、水および塩水で連続して洗浄し、Ｎａ₂ＳＯ₄上で乾燥させ、ろ過し、減圧下で濃縮した。粗生成物をジクロロメタンに溶解させ、ＴＥＦＬＯＮ ＢＵＬＫ ＳＯＲＢＥＮＴＳ上に吸着させた。シクロヘキサン／ＥｔＯＡｃで溶離しながらの、シリカゲルカートリッジ（Ｒｆ２００）上での精製により、表題化合物がベージュ色の樹脂として得られた。ＬＣＭＳ（方法３）：２９５（Ｍ＋Ｈ）⁺；保持時間：０．７２分。¹Ｈ ＮＭＲ（４００ＭＨｚ、ＣＤＣｌ₃）δ ｐｐｍ：１．３６（ｔ，Ｊ＝７．５Ｈｚ、３Ｈ）、１．５７−１．６２（ｍ，２Ｈ）、１．９５−２．００（ｍ，２Ｈ）、２．０５（ｓ，２Ｈ）、４．０４（ｓ，４Ｈ）、８．１３（ｄ，Ｊ＝２．２０Ｈｚ、１Ｈ）、８．８７（ｄ，Ｊ＝２．２０Ｈｚ、１Ｈ）． Step 6: Preparation of methyl 5- (1-cyanocyclopropyl) -3-ethylsulfonyl-pyridine-2-carboxylate

Methyl 5- (cyanomethyl) -3-ethylsulfonyl-pyridine-2-carboxylate (0.63 g, 2.3 mmol) was dissolved in acetonitrile (19 mL) and cesium carbonate (2.3 g, 7.0 mmol) was dissolved in colorless. After addition to the solution (the solution darkened), 1,2-dibromoethane (0.90 g, 0.41 mL, 4.7 mmol) was added. The brown solution was stirred at a bath temperature of 80 ° C. The desired mass was detected by LC / MS at Rt = 0.73 minutes after 1.5 hours. The reaction mixture was concentrated under reduced pressure and diluted with EtOAc and water. The organic layer was separated, washed successively with water and brine, dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The crude product was dissolved in dichloromethane and adsorbed on TEFLON BULK SORBENTS. Purification on a silica gel cartridge (Rf200) eluting with cyclohexane / EtOAc gave the title compound as a beige resin. LCMS (Method 3): 295 (M + H) ⁺ ; Retention time: 0.72 minutes. ¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 1.36 (t, J = 7.5 Hz, 3H), 1.57-1.62 (m, 2H), 1.95-2.00 (m, 2H), 2.05 (s, 2H), 4.04 (s, 4H), 8.13 (d, J = 2.20 Hz, 1H), 8.87 (d, J = 2.20 Hz, 1H) .

メチル５−（１−シアノシクロプロピル）−３−エチルスルホニル−ピリジン−２−カルボキシレート（０．２７ｇ、０．９２ｍｍｏｌ）の溶液をＴＨＦ（４ｍＬ）および水（１．５ｍＬ）に溶解させ（赤色の溶液）、次に、ＬｉＯＨ・Ｈ₂Ｏ（０．０５８ｇ、１．４ｍｍｏｌ）で処理した。混合物を周囲温度で２時間撹拌し、それまでにＬＣＭＳ分析により反応の完了が示された（Ｒｔ＝０．３２分で所望の生成物のみ、方法３）。ＴＨＦを減圧下で蒸発させ、残渣を１ＭのＨＣｌで酸性化し、ＥｔＯＡｃで抽出した。有機層を塩水で洗浄し、Ｎａ₂ＳＯ₄上で乾燥させ、ろ過し、減圧下で濃縮したところ、純粋な表題生成物がベージュ色の固体として得られた。ＬＣＭＳ（方法３）：２８１（Ｍ＋Ｈ）⁺；保持時間：０．３０分。¹Ｈ ＮＭＲ（４００ＭＨｚ、メタノール−ｄ₄）δ ｐｐｍ：１．３１（ｔ，Ｊ＝７．３Ｈｚ、３Ｈ）、１．７１−１．７８（ｍ，２Ｈ）、１．９２−１．９８（ｍ，２Ｈ）、３．６０（ｑ，Ｊ＝７．３Ｈｚ、２Ｈ）、８．２８（ｄ，Ｊ＝２．２０Ｈｚ、１Ｈ）、８．８３（ｄ，Ｊ＝２．２０Ｈｚ、１Ｈ）． Step 7: Preparation of 5- (1-cyanocyclopropyl) -3-ethylsulfonyl-pyridine-2-carboxylic acid

A solution of methyl 5- (1-cyanocyclopropyl) -3-ethylsulfonyl-pyridine-2-carboxylate (0.27 g, 0.92 mmol) was dissolved in THF (4 mL) and water (1.5 mL) (red). Solution) followed by LiOH.H ₂ O (0.058 g, 1.4 mmol). The mixture was stirred at ambient temperature for 2 hours, by which time LCMS analysis showed that the reaction was complete (only desired product, method 3 at Rt = 0.32 min). The THF was evaporated under reduced pressure and the residue was acidified with 1M HCl and extracted with EtOAc. The organic layer was washed with brine, dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give the pure title product as a beige solid. LCMS (Method 3): 281 (M + H) ⁺ ; Retention time: 0.30 min. ¹ H NMR (400 MHz, methanol-d ₄ ) δ ppm: 1.31 (t, J = 7.3 Hz, 3H), 1.71-1.78 (m, 2H), 1.92-1.98 ( m, 2H), 3.60 (q, J = 7.3 Hz, 2H), 8.28 (d, J = 2.20 Hz, 1H), 8.83 (d, J = 2.20 Hz, 1H).

（ａ）５−（１−シアノシクロプロピル）−３−エチルスルホニル−ピリジン−２−カルボニルクロリド：実施例Ｐ１、工程１の手順に従って、ジクロロメタン（１５ｍｌ）中の５−（１−シアノ−シクロプロピル）−３−エチルスルホニル−ピリジン−２−カルボン酸（１．０ｇ、３．５７ｍｍｏｌ）および塩化オキサリル（０．４０５ｍｌ、４．６４ｍｍｏｌ）から得られた。混合物を周囲温度で２時間撹拌し、次に、蒸発乾固させたところ、酸塩化物（１．０６ｇ）が固体として得られた。 Step 8: Preparation of 5- (1-cyanocyclopropyl) -3-ethylsulfonyl-N- [2- (methylamino) -5- (trifluoromethyl) -3-pyridyl] pyridine-2-carboxamide

(A) 5- (1-Cyanocyclopropyl) -3-ethylsulfonyl-pyridine-2-carbonyl chloride: 5- (1-cyano-cyclopropyl in dichloromethane (15 ml) according to the procedure of Example P1, Step 1. ) -3-Ethylsulfonyl-pyridine-2-carboxylic acid (1.0 g, 3.57 mmol) and oxalyl chloride (0.405 ml, 4.64 mmol). The mixture was stirred at ambient temperature for 2 hours and then evaporated to dryness to give the acid chloride (1.06 g) as a solid.

(B) N2-methyl-5- (trifluoromethyl) pyridine-2,3-diamine (600 mg, 3.14 mmol) and triethylamine (1.09 ml, 7.85 mmol) in dichloromethane (24 ml) at 0-5 ° C. To this solution was added dropwise a solution of 5- (1-cyanocyclopropyl) -3-ethylsulfonyl-pyridine-2-carbonyl chloride (1.03 g, 3.45 mmol) in dichloromethane (4 ml). The reaction mixture was stirred at 0-5 ° C. for 30 minutes and then at ambient temperature overnight. Water was added to the mixture and the aqueous layer was extracted 3 times with dichloromethane. The combined organic layers were washed with water and brine, dried over Na ₂ SO ₄ , filtered and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel to give the title compound 5- (1-cyanocyclopropyl) -3-ethylsulfonyl-N- [2- (methylamino) -5- (trifluoro-methyl). ) -3-Pyridyl] pyridine-2-carboxamide (1.1 g) was obtained as a solid. LCMS (Method 3): 454 (M + H) +; Retention time: 0.91 min. ¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 1.4 (t, J = 7 Hz, 3H), 1.6-1.7 (m, 2H), 2.0-2.1 (m, 2H) 3.1 (d, J = 5 Hz, 3H), 3.9 (q, J = 7 Hz, 2H), 5.5 (d, J = 4 Hz, 1H), 7.7 (d, J = 4 Hz, 1H), 8.2 (d, J = 2 Hz, 1H), 8.3 (s, 1H), 8.4 (s, 1H), 8.9 (d, J = 3 Hz, 1H).

氷酢酸（１．５ｍＬ）中の５−（１−シアノシクロプロピル）−３−エチルスルホニル−Ｎ−［２−（メチルアミノ）−５−（トリフルオロメチル）−３−ピリジル］ピリジン−２−カルボキサミド（６２ｍｇ、０．１３７ｍｍｏｌ）の溶液を２０分間にわたり１５０℃においてマイクロ波中で加熱した。反応混合物を水（１０ｍｌ）に注ぎ、得られた懸濁液を周囲温度で２０分間撹拌した。形成された沈殿物をろ過し、水で３回洗浄した。固体を５０℃において減圧下で乾燥させたところ、表題化合物１−［５−エチルスルホニル−６−［３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン−２−イル］−３−ピリジル］シクロプロパン−カルボニトリル（化合物Ｐ９）が白色の固体（４０ｍｇ）として得られた（融点１７１〜１７３℃）。ＬＣＭＳ（方法３）：４３６（Ｍ＋Ｈ）＋；保持時間：０．９８分。¹Ｈ ＮＭＲ（４００ＭＨｚ、ＣＤＣｌ₃）δ ｐｐｍ：１．４（ｔ，Ｊ＝７Ｈｚ、３Ｈ）、１．７−１．７（ｍ，２Ｈ）、２．０−２．１（ｍ，２Ｈ）、３．９−４．０（ｑ，２Ｈ）、３．９３（ｓ，３Ｈ）、８．３（ｄ，Ｊ＝２Ｈｚ、１Ｈ）、８．３（ｄ，Ｊ＝１Ｈｚ、１Ｈ）、８．８（ｄ，Ｊ＝１Ｈｚ、１Ｈ）、９．１（ｄ，Ｊ＝２Ｈｚ、１Ｈ）． Step 9: 1- [5-Ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl] -3-pyridyl] cyclopropanecarbonitrile (compound Preparation of P9)

5- (1-Cyanocyclopropyl) -3-ethylsulfonyl-N- [2- (methylamino) -5- (trifluoromethyl) -3-pyridyl] pyridine-2-in glacial acetic acid (1.5 mL) A solution of carboxamide (62 mg, 0.137 mmol) was heated in the microwave at 150 ° C. for 20 minutes. The reaction mixture was poured into water (10 ml) and the resulting suspension was stirred at ambient temperature for 20 minutes. The formed precipitate was filtered and washed 3 times with water. The solid was dried at 50 ° C. under reduced pressure to give the title compound 1- [5-ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl. ] -3-Pyridyl] cyclopropane-carbonitrile (Compound P9) was obtained as a white solid (40 mg) (mp 171-173 ° C.). LCMS (Method 3): 436 (M + H) +; Retention time: 0.98 min. ¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 1.4 (t, J = 7 Hz, 3H), 1.7-1.7 (m, 2H), 2.0-2.1 (m, 2H) 3.9-4.0 (q, 2H), 3.93 (s, 3H), 8.3 (d, J = 2 Hz, 1H), 8.3 (d, J = 1 Hz, 1H), 8 .8 (d, J = 1 Hz, 1H), 9.1 (d, J = 2 Hz, 1H).

周囲温度でメタノール（４ｍＬ）中の１−［５−エチルスルホニル−６−［３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン−２−イル］−３−ピリジル］シクロプロパンカルボニトリル（９０ｍｇ、０．２０７ｍｍｏｌ）の懸濁液に水酸化ナトリウム（０．２５８ｍＬ、１．０３４ｍｍｏｌ）の４Ｍの水溶液を加えた。反応混合物を６０℃で５時間および周囲温度で一晩撹拌した。混合物を減圧下で蒸発させ、残渣をジクロロメタンに溶解させた。水を加え、層を分離し、水相をジクロロメタンで３回抽出した。組み合わされた有機層を塩水で洗浄し、Ｎａ₂ＳＯ₄上で乾燥させ、ろ過し、蒸発させた。粗生成物をシリカゲル上でのフラッシュクロマトグラフィーによって精製したところ、１−［５−エチルスルホニル−６−［３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン−２−イル］−３−ピリジル］シクロプロパンカルボキサミド（化合物Ｐ１１）が固体（３５ｍｇ）として得られた（融点２１５〜２１７℃）。ＬＣＭＳ（方法３）：４５４（Ｍ＋Ｈ）＋；保持時間：０．８７分。¹Ｈ ＮＭＲ（４００ＭＨｚ、ＣＤＣｌ₃）δ ｐｐｍ：１．３−１．４（ｍ，２Ｈ）、１．４−１．５（ｔ，３Ｈ）、１．８−１．９（ｍ，２Ｈ）、３．９−３．９（ｑ，２Ｈ）、４．０（ｓ，３Ｈ）、５．３（ｂｒ ｓ，１Ｈ）、５．７（ｂｒ ｓ，１Ｈ）、８．３（ｄ，Ｊ＝１Ｈｚ、１Ｈ）、８．６（ｄ，Ｊ＝２Ｈｚ、１Ｈ）、８．８（ｄ，Ｊ＝１Ｈｚ、１Ｈ）、９．１（ｄ，Ｊ＝２Ｈｚ、１Ｈ）． Example P6: 1- [5-Ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl] -3-pyridyl] cyclopropanecarboxamide (compound Preparation of P11)

1- [5-Ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl] -3-pyridyl] in methanol (4 mL) at ambient temperature To a suspension of cyclopropanecarbonitrile (90 mg, 0.207 mmol) was added a 4M aqueous solution of sodium hydroxide (0.258 mL, 1.034 mmol). The reaction mixture was stirred at 60 ° C. for 5 hours and at ambient temperature overnight. The mixture was evaporated under reduced pressure and the residue was dissolved in dichloromethane. Water was added, the layers were separated and the aqueous phase was extracted 3 times with dichloromethane. The combined organic layers were washed with brine, dried over Na ₂ SO ₄ , filtered and evaporated. The crude product was purified by flash chromatography on silica gel to give 1- [5-ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine-2- Yl] -3-pyridyl] cyclopropanecarboxamide (Compound P11) was obtained as a solid (35 mg) (mp 215-217 ° C.). LCMS (Method 3): 454 (M + H) +; Retention time: 0.87 minutes. ¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 1.3-1.4 (m, 2H), 1.4-1.5 (t, 3H), 1.8-1.9 (m, 2H) 3.9-3.9 (q, 2H), 4.0 (s, 3H), 5.3 (br s, 1H), 5.7 (br s, 1H), 8.3 (d, J = 1 Hz, 1 H), 8.6 (d, J = 2 Hz, 1 H), 8.8 (d, J = 1 Hz, 1 H), 9.1 (d, J = 2 Hz, 1 H).

１，２−ジメトキシエタン（４ｍｌ）中の２−（６−クロロ−３−エチルスルホニル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（２５０ｍｇ、０．６１８ｍｍｏｌ）、２Ｍの炭酸ナトリウム水溶液（０．９２６ｍｌ、１．８５３ｍｍｏｌ）およびシクロプロピルボロン酸（１０６ｍｇ、１．２３５ｍｍｏｌ）の溶液を１０分間にわたってアルゴンでパージした。ビス（トリフェニルホスフィン）パラジウム（ＩＩ）ジクロリド（４．３ｍｇ、０．０１当量）を加え、混合物を４０分間にわたり１１０℃においてマイクロ波中で加熱した。混合物を酢酸エチルで希釈し、水で（３回）洗浄し、組み合わされた有機相を塩水で洗浄し、硫酸ナトリウム上で乾燥させ、ろ過し、蒸発させた。残渣をシリカゲル上でのカラムクロマトグラフィー（シクロヘキサン／酢酸エチル１：１）によって精製したところ、表題化合物Ｐ１４が固体として得られた（融点１６３〜１６５℃）。ＬＣＭＳ（方法３）：４１１（Ｍ＋Ｈ）⁺；保持時間：１．０７分。¹Ｈ ＮＭＲ（４００ＭＨｚ、ＣＤＣｌ₃）δ ｐｐｍ：１．１８（ｍ，４Ｈ）、１．３５（ｔ，３Ｈ）、２．２１（ｍ，１Ｈ）、３．７７（ｑ，２Ｈ）、３．８３（ｓ，３Ｈ）、７．５２（ｄ，Ｊ＝８．４４Ｈｚ、１Ｈ）、８．２９（ｓ，１Ｈ）、８．３１（ｄ，Ｊ＝８．４４Ｈｚ、１Ｈ）、８．７５（ｓ，１Ｈ）． Example P7: Preparation of 2- (6-cyclopropyl-3-ethylsulfonyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (Compound P14)

2- (6-Chloro-3-ethylsulfonyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (250 mg) in 1,2-dimethoxyethane (4 ml) , 0.618 mmol), a solution of 2M aqueous sodium carbonate (0.926 ml, 1.853 mmol) and cyclopropylboronic acid (106 mg, 1.235 mmol) was purged with argon for 10 min. Bis (triphenylphosphine) palladium (II) dichloride (4.3 mg, 0.01 eq) was added and the mixture was heated in the microwave at 110 ° C. for 40 minutes. The mixture was diluted with ethyl acetate and washed with water (3 times) and the combined organic phases were washed with brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by column chromatography on silica gel (cyclohexane / ethyl acetate 1: 1) to give the title compound P14 as a solid (melting point 163-165 ° C.). LCMS (Method 3): 411 (M + H) ⁺ ; Retention time: 1.07 minutes. ¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 1.18 (m, 4H), 1.35 (t, 3H), 2.21 (m, 1H), 3.77 (q, 2H), 3. 83 (s, 3H), 7.52 (d, J = 8.44 Hz, 1H), 8.29 (s, 1H), 8.31 (d, J = 8.44 Hz, 1H), 8.75 ( s, 1H).

周囲温度でメタノール（４ｍＬ）中の１−［５−エチルスルホニル−６−［３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン−２−イル］−３−ピリジル］シクロプロパンカルボニトリル（９０ｍｇ、０．２０７ｍｍｏｌ）の懸濁液に水酸化ナトリウム（０．２５８ｍＬ、１．０３４ｍｍｏｌ）の４Ｍの水溶液を加えた。反応混合物を６０℃で５時間および周囲温度で一晩撹拌した。混合物を減圧下で蒸発させ、残渣をジクロロメタンに溶解させた。水を加え、層を分離し、水相をジクロロメタンで３回抽出した。水層をｐＨ１になるまで酸性化し、ジクロロメタンで抽出した。有機層をＮａ₂ＳＯ₄上で乾燥させ、ろ過し、蒸発させたところ、１−［５−エチルスルホニル−６−［３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン−２−イル］−３−ピリジル］シクロプロパンカルボン酸（化合物Ｐ１２）がガムとして得られた。ＬＣＭＳ（方法３）：４５５（Ｍ＋Ｈ）＋；保持時間：０．９１分。
¹Ｈ ＮＭＲ（４００ＭＨｚ、ＣＤＣｌ₃）δ ｐｐｍ：１．３（ｔ，Ｊ＝７Ｈｚ、３Ｈ）、１．４−１．５（ｍ，２Ｈ）、１．９−２．０（ｍ，２Ｈ）、３．６（ｑ，Ｊ＝７Ｈｚ、２Ｈ）、３．９（ｓ，３Ｈ）、５．３（ｓ，１Ｈ）、８．４（ｄ，Ｊ＝２Ｈｚ、１Ｈ）、８．５（ｄ，Ｊ＝１Ｈｚ、１Ｈ）、８．８（ｄ，Ｊ＝１Ｈｚ、１Ｈ）、８．９（ｄ，Ｊ＝２Ｈｚ、１Ｈ）． Example P8: 1- [5-ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl] -3-pyridyl] cyclopropanecarboxylic acid ( Preparation of compound P12)

1- [5-Ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl] -3-pyridyl] in methanol (4 mL) at ambient temperature To a suspension of cyclopropanecarbonitrile (90 mg, 0.207 mmol) was added a 4M aqueous solution of sodium hydroxide (0.258 mL, 1.034 mmol). The reaction mixture was stirred at 60 ° C. for 5 hours and at ambient temperature overnight. The mixture was evaporated under reduced pressure and the residue was dissolved in dichloromethane. Water was added, the layers were separated and the aqueous phase was extracted 3 times with dichloromethane. The aqueous layer was acidified to pH 1 and extracted with dichloromethane. The organic layer was dried over Na ₂ SO ₄ , filtered and evaporated to give 1- [5-ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b]. Pyridin-2-yl] -3-pyridyl] cyclopropanecarboxylic acid (Compound P12) was obtained as a gum. LCMS (Method 3): 455 (M + H) +; Retention time: 0.91 min.
¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 1.3 (t, J = 7 Hz, 3H), 1.4-1.5 (m, 2H), 1.9-2.0 (m, 2H) 3.6 (q, J = 7 Hz, 2H), 3.9 (s, 3H), 5.3 (s, 1H), 8.4 (d, J = 2 Hz, 1H), 8.5 (d , J = 1 Hz, 1 H), 8.8 (d, J = 1 Hz, 1 H), 8.9 (d, J = 2 Hz, 1 H).

０〜５℃で酢酸エチル（５ｍｌ）中のＮ２−メチル−５−（トリフルオロメチルスルファニル）ピリジン−２，３−ジアミン（１００ｍｇ、０．４４８ｍｍｏｌ）およびトリエチルアミン（０．１５８ｍｌ、１．１２ｍｍｏｌ）の溶液にテトラヒドロフラン（３ｍｌ）中の５−（１−シアノシクロプロピル）−３−エチルスルホニル−ピリジン−２−カルボニルクロリド［ジクロロメタン（５ｍｌ）中の５−（１−シアノシクロプロピル）−３−エチルスルホニル−ピリジン−２−カルボン酸（１２６ｍｇ、０．４４８ｍｍｏｌ）および塩化オキサリル（０．０７１８ｍｌ、０．８０６ｍｍｏｌ）から、実施例Ｐ５、工程８（ａ）に従って調製された］の溶液を滴下して加えた。反応混合物を周囲温度で３０分間撹拌した。懸濁液をＮａＨＣＯ₃水溶液に注ぎ、混合物を酢酸エチルで抽出した。組み合わされた有機層を１ＮのＨＣｌ水溶液および塩水で洗浄し、硫酸マグネシウム上で乾燥させ、ろ過し、減圧下で濃縮したところ、５−（１−シアノシクロプロピル）−３−エチルスルホニル−Ｎ−［２−（メチルアミノ）−５−（トリフルオロメチルスルファニル）−３−ピリジル］ピリジン−２−カルボキサミドが固体として得られた。この材料をさらに精製せずに使用した。ＬＣＭＳ（方法３）：４８６（Ｍ＋Ｈ）＋；保持時間：０．９７分。 Example P9: 1- [5-ethylsulfonyl-6- [3-methyl-6- (trifluoromethylsulfanyl) imidazo [4,5-b] pyridin-2-yl] -3-pyridyl] cyclopropanecarbonitrile (Compound P13) Preparation Step 1: 5- (1-Cyanocyclopropyl) -3-ethylsulfonyl-N- [2- (methylamino) -5- (trifluoromethylsulfanyl) -3-pyridyl] pyridine-2 -Preparation of carboxamide

Of N2-methyl-5- (trifluoromethylsulfanyl) pyridine-2,3-diamine (100 mg, 0.448 mmol) and triethylamine (0.158 ml, 1.12 mmol) in ethyl acetate (5 ml) at 0-5 <0> C. To the solution was added 5- (1-cyanocyclopropyl) -3-ethylsulfonyl-pyridine-2-carbonyl chloride [5- (1-cyanocyclopropyl) -3-ethylsulfonyl in dichloromethane (5 ml) in tetrahydrofuran (3 ml). -Prepared according to Example P5, step 8 (a) from pyridine-2-carboxylic acid (126 mg, 0.448 mmol) and oxalyl chloride (0.0718 ml, 0.806 mmol)] was added dropwise. . The reaction mixture was stirred at ambient temperature for 30 minutes. The suspension was poured into aqueous NaHCO ₃ and the mixture was extracted with ethyl acetate. The combined organic layers were washed with 1N aqueous HCl and brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 5- (1-cyanocyclopropyl) -3-ethylsulfonyl-N—. [2- (Methylamino) -5- (trifluoromethylsulfanyl) -3-pyridyl] pyridine-2-carboxamide was obtained as a solid. This material was used without further purification. LCMS (Method 3): 486 (M + H) +; Retention time: 0.97 minutes.

実施例Ｐ５、工程９に従って、氷酢酸（２．６ｍｌ）中の５−（１−シアノシクロプロピル）−３−エチルスルホニル−Ｎ−［２−（メチルアミノ）−５−（トリフルオロメチルスルファニル）−３−ピリジル］ピリジン−２−カルボキサミド（２１８ｍｇ、０．４４８ｍｍｏｌ）から得られた。溶液を３０分間にわたり１５０℃においてマイクロ波中で加熱した。反応混合物を水に注ぎ、１ＮのＮａＯＨ水溶液を沈殿物が形成されるまで加えた。固体をろ過し、減圧下で乾燥させ、次に、シリカゲル上でのカラムクロマトグラフィー（シクロヘキサン中０〜３５％の酢酸エチルの勾配）によって精製したところ、１−［５−エチルスルホニル−６−［３−メチル−６−（トリフルオロ−メチルスルファニル）イミダゾ［４，５−ｂ］ピリジン−２−イル］−３−ピリジル］シクロプロパンカルボニトリル（化合物Ｐ１３）が固体として得られた（融点１７２．３〜１７２．５）。ＬＣＭＳ（方法３）：４６８（Ｍ＋Ｈ）＋；保持時間：１．０３分。
¹Ｈ ＮＭＲ（４００ＭＨｚ、ＣＤＣｌ₃）δ ｐｐｍ：１．３８（ｔ，Ｊ＝７．５２Ｈｚ、３Ｈ）、１．６５−１．７１（ｍ，２Ｈ）、２．０１−２．０８（ｍ，２Ｈ）、３．８８（ｓ，３Ｈ）、３．９１（ｑ，Ｊ＝７．５２Ｈｚ、２Ｈ）、８．２５（ｄ，Ｊ＝２．２０Ｈｚ、１Ｈ）、８．３７（ｄ，Ｊ＝１．８３Ｈｚ、１Ｈ）、８．７１（ｄ，Ｊ＝１．８３Ｈｚ、１Ｈ）、９．０５（ｄ，Ｊ＝２．２０Ｈｚ、１Ｈ）． Step 2: 1- [5-Ethylsulfonyl-6- [3-methyl-6- (trifluoromethylsulfanyl) imidazo [4,5-b] pyridin-2-yl] -3-pyridyl] cyclopropanecarbonitrile ( Preparation of compound P13)

According to Example P5, Step 9, 5- (1-cyanocyclopropyl) -3-ethylsulfonyl-N- [2- (methylamino) -5- (trifluoromethylsulfanyl) in glacial acetic acid (2.6 ml) Obtained from -3-pyridyl] pyridine-2-carboxamide (218 mg, 0.448 mmol). The solution was heated in the microwave at 150 ° C. for 30 minutes. The reaction mixture was poured into water and 1N aqueous NaOH was added until a precipitate formed. The solid was filtered and dried under reduced pressure, then purified by column chromatography on silica gel (gradient of 0-35% ethyl acetate in cyclohexane) to give 1- [5-ethylsulfonyl-6- [ 3-Methyl-6- (trifluoro-methylsulfanyl) imidazo [4,5-b] pyridin-2-yl] -3-pyridyl] cyclopropanecarbonitrile (Compound P13) was obtained as a solid (melting point 172. 3-172.5). LCMS (Method 3): 468 (M + H) +; Retention time: 1.03 minutes.
¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 1.38 (t, J = 7.52 Hz, 3H), 1.65-1.71 (m, 2H), 2.01-2.08 (m, 2H), 3.88 (s, 3H), 3.91 (q, J = 7.52 Hz, 2H), 8.25 (d, J = 2.20 Hz, 1H), 8.37 (d, J = 1.83 Hz, 1H), 8.71 (d, J = 1.83 Hz, 1H), 9.05 (d, J = 2.20 Hz, 1H).

ＤＭＦ（５ｍｌ）中の２−（６−クロロ−３−エチルスルホニル−２−ピリジル）−３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン（５００ｍｇ、１．２３５ｍｍｏｌ）の溶液を１０分間にわたってアルゴンでパージし、次に、アルゴン下でＴＭＳ−アセトニトリル（２１０ｍｇ、０．２５４ｍｌ、１．８５３ｍｍｏｌ）、ジフルオロ亜鉛（７６．６ｍｇ、０．７４１ｍｍｏｌ）、キサントホス（２８．６ｍｇ、０．０４９ｍｍｏｌ）およびＰｄ₂（ｄｂａ）₃（２２．６ｍｇ、０．０２５ｍｍｏｌ）で処理した。得られた混合物を３０分間にわたり１４０℃においてマイクロ波中で加熱した。反応混合物を冷却し、酢酸エチルで希釈し、ｈｙｆｌｏ上でろ過した。ろ液を水および塩水で洗浄し、硫酸ナトリウム上で乾燥させ、ろ過し、減圧下で蒸発させた。残渣をシリカゲル上でのフラッシュカラムクロマトグラフィー（ジクロロメタン／酢酸エチル５：１）によって精製したところ、２−［５−エチルスルホニル−６−［３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン−２−イル］−２−ピリジル］アセトニトリルが固体として得られた。ＬＣＭＳ（方法３）：４１０（Ｍ＋Ｈ）＋；保持時間：０．９１分。¹Ｈ ＮＭＲ（４００ＭＨｚ、ＣＤＣｌ₃）δ ｐｐｍ：１．３８（ｔ，Ｊ＝７．５２Ｈｚ、３Ｈ）、３．８６（ｑ，Ｊ＝７．５２Ｈｚ、２Ｈ）、３．９２（ｓ，３Ｈ）、４．１３（ｓ，２Ｈ）、７．８４（ｄ，Ｊ＝８．０７Ｈｚ、１Ｈ）、８．３２（ｄ，Ｊ＝１．４７Ｈｚ、１Ｈ）、８．６０（ｄ，Ｊ＝８．０７Ｈｚ、１Ｈ）、８．７８（ｄ，Ｊ＝１．４７Ｈｚ、１Ｈ）． Example P10: 1- [5-ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl] -2-pyridyl] cyclopropanecarbonitrile ( Preparation step 1 of compound P15) 1: 2- [5-ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl] -2-pyridyl] acetonitrile Preparation of

2- (6-Chloro-3-ethylsulfonyl-2-pyridyl) -3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridine (500 mg, 1.235 mmol) in DMF (5 ml) Was purged with argon for 10 minutes, then TMS-acetonitrile (210 mg, 0.254 ml, 1.853 mmol), difluorozinc (76.6 mg, 0.741 mmol), xanthophos (28.6 mg, under argon). 0.049 mmol) and Pd ₂ (dba) ₃ (22.6 mg, 0.025 mmol). The resulting mixture was heated in the microwave at 140 ° C. for 30 minutes. The reaction mixture was cooled, diluted with ethyl acetate and filtered over hyflo. The filtrate was washed with water and brine, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel (dichloromethane / ethyl acetate 5: 1) to give 2- [5-ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4 5-b] pyridin-2-yl] -2-pyridyl] acetonitrile was obtained as a solid. LCMS (Method 3): 410 (M + H) +; Retention time: 0.91 min. ¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 1.38 (t, J = 7.52 Hz, 3H), 3.86 (q, J = 7.52 Hz, 2H), 3.92 (s, 3H) 4.13 (s, 2H), 7.84 (d, J = 8.07 Hz, 1H), 8.32 (d, J = 1.47 Hz, 1H), 8.60 (d, J = 8. 07 Hz, 1H), 8.78 (d, J = 1.47 Hz, 1H).

アセトニトリル（２．５５ｍｌ）中の２−［５−エチルスルホニル−６−［３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン−２−イル］−２−ピリジル］アセトニトリル（１００ｍｇ、０．２４４ｍｍｏｌ）および炭酸セシウム（２４０ｍｇ、０．７３３ｍｍｏｌ）の溶液に１，２−ジブロモエタン（９２ｍｇ、０．０４２ｍｌ、０．４８９ｍｍｏｌ）を加えた。反応混合物を８０℃で３０分間加熱し、次に、減圧下で濃縮した。混合物を酢酸エチルおよび水で希釈し、層を分離し、有機相を水で（３回）および塩水で洗浄し、硫酸ナトリウム上で乾燥させ、ろ過し、蒸発させた。残渣をシリカゲル上でのカラムクロマトグラフィー（シクロヘキサン／酢酸エチル２：１）によって精製したところ、１−［５−エチルスルホニル−６−［３−メチル−６−（トリフルオロメチル）イミダゾ［４，５−ｂ］ピリジン−２−イル］−２−ピリジル］シクロプロパンカルボニトリル（化合物Ｐ１５）がガムとして得られた。ＬＣＭＳ（方法３）：４３６（Ｍ＋Ｈ）＋；保持時間：１．０１分。¹Ｈ ＮＭＲ（４００ＭＨｚ、ＣＤＣｌ₃）δ ｐｐｍ：１．３６（ｔ，Ｊ＝７．５２Ｈｚ、３Ｈ）、１．９２（ｍ，４Ｈ）、３．７８（ｑ，Ｊ＝７．５２Ｈｚ、２Ｈ）、３．８１（ｓ，３Ｈ）、８．１２（ｄ，Ｊ＝８．４１Ｈｚ、１Ｈ）、８．３０（ｄ，Ｊ＝１．４７Ｈｚ、１Ｈ）、８．５２（ｄ，Ｊ＝８．４１Ｈｚ、１Ｈ）、８．７７（ｄ，Ｊ＝１．８３、１．４７Ｈｚ、１Ｈ）． Step 2: 1- [5-Ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl] -2-pyridyl] cyclopropanecarbonitrile (compound Preparation of P15)

2- [5-Ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5-b] pyridin-2-yl] -2-pyridyl] acetonitrile in acetonitrile (2.55 ml) To a solution of (100 mg, 0.244 mmol) and cesium carbonate (240 mg, 0.733 mmol) was added 1,2-dibromoethane (92 mg, 0.042 ml, 0.489 mmol). The reaction mixture was heated at 80 ° C. for 30 minutes and then concentrated under reduced pressure. The mixture was diluted with ethyl acetate and water, the layers were separated, the organic phase was washed with water (3 times) and brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by column chromatography on silica gel (cyclohexane / ethyl acetate 2: 1) to give 1- [5-ethylsulfonyl-6- [3-methyl-6- (trifluoromethyl) imidazo [4,5 -B] Pyridin-2-yl] -2-pyridyl] cyclopropanecarbonitrile (Compound P15) was obtained as a gum. LCMS (Method 3): 436 (M + H) +; Retention time: 1.01 min. ¹ H NMR (400 MHz, CDCl ₃ ) δ ppm: 1.36 (t, J = 7.52 Hz, 3H), 1.92 (m, 4H), 3.78 (q, J = 7.52 Hz, 2H) 3.81 (s, 3H), 8.12 (d, J = 8.41 Hz, 1H), 8.30 (d, J = 1.47 Hz, 1H), 8.52 (d, J = 8. 41 Hz, 1H), 8.77 (d, J = 1.83, 1.47 Hz, 1H).

Table P: Examples of compounds of formula (I) The compounds in Table P may be prepared as described in the above examples or in a similar manner.

Table P (continued): Examples of compounds of formula (I)

  The activity of the composition according to the invention can be considerably expanded and adapted to the general situation by adding other insecticidal, acaricidal and / or fungicidal active ingredients. . A further surprising advantage is that the mixture of the compound of formula I with other insecticidal, acaricidal and / or fungicidal active ingredients may be described in a broader sense as synergistic activity May also have. For example, better tolerance by plants, reduced phytotoxicity, that insects can be controlled at their different stages of development, or during their production, e.g. during grinding or mixing, during their storage or during their use There is better behavior.

  Suitable additives to the active ingredients herein are typically exemplified by the following types of active ingredients: organophosphorus compounds, nitrophenol derivatives, thiourea, juvenile hormone, formamidine, benzophenone derivatives, urea , Pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridylmethyleneamino derivatives, macrolides, neonicotinoids and Bacillus thuringiensis preparations.

Preferred are the following mixtures of a compound of formula I and an active ingredient (the abbreviation “TX” is “one compound selected from the group consisting of the compounds described in Tables 1-18 and Table P of the invention”) Means):
An adjuvant selected from the group of substances consisting of petroleum (628) + TX,
1,1-bis (4-chlorophenyl) -2-ethoxyethanol (IUPAC name) (910) + TX, 2,4-dichlorophenylbenzenesulfonate (IUPAC / chemical abstract name) (1059) + TX, 2-fluoro-N -Methyl-N-1-naphthylacedoamide (IUPAC name) (1295) + TX, 4-chlorophenylphenylsulfone (IUPAC name) (981) + TX, abamectin (1) + TX, acequinosyl (3) + TX, acetoprole [CCN ] + TX, Acrinatrin (9) + TX, Aldicarb (16) + TX, Aldoxycarb (863) + TX, α-Cypermethrin (202) + TX, Amidithione (870) + TX, Amidoflumet [CCN] + TX, Amidothioate (872) + TX, Amit (875) + TX, Amiton hydrogen oxalate (875) + TX, Amitraz (24) + TX, Aramite (881) + TX, Arsenic trioxide (882) + TX, AVI 382 (Compound code) + TX, AZ 60541 (Compound code) + TX Azinphos-ethyl (44) + TX, Azinphos-methyl (45) + TX, Azobenzene (IUPAC name) (888) + TX, Azocyclotin (46) + TX, Azotoate (889) + TX, Benomyl (62) + TX, Benoxaphos [CCN] + TX , Benzoximate (71) + TX, benzyl benzoate (IUPAC name) [CCN] + TX, biphenazate (74) + TX, bifenthrin (76) + TX, binapacryl (907) + TX, brofenvalerate + TX, bromocyclene (91 ) + TX, bromophos (920) + TX, bromophos-ethyl (921) + TX, bromopropylate (94) + TX, buprofezin (99) + TX, butcarboxyme (103) + TX, butoxycarboxyme (104) + TX, butylpyridaben + TX , Calcium polysulfide (IUPAC name) (111) + TX, camphorchlor (941) + TX, carbanolate (943) + TX, carbaryl (115) + TX, carbofuran (118) + TX, carbophenothione (947) + TX, CGA 50'439 ( Development code) (125) + TX, quinomethionato (126) + TX, chlorbenside (959) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorfenapyr (130) + TX, Lorphenetol (968) + TX, chlorfenson (970) + TX, chlorfen sulfide (971) + TX, chlorfenvinphos (131) + TX, chlorobenzilate (975) + TX, chloromebuform (977) + TX, chloromethyuron (978) + TX , Chloropropylate (983) + TX, chlorpyrifos (145) + TX, chlorpyrifos-methyl (146) + TX, chlorothiophos (994) + TX, cineline I (696) + TX, cineline II (696) + TX, cineline (696) + TX, chloro Fentedine (158) + TX, Closantel [CCN] + TX, Coumaphos (174) + TX, Crotamiton [CCN] + TX, Crotoxyfos (1010) + TX, Cufraneb (1013) + TX, Cyanto (1020) + TX, cyflumetofen (CAS registration number: 400082-07-7) + TX, cyhalothrin (196) + TX, cyhexatin (199) + TX, cypermethrin (201) + TX, DCPM (1032) + TX, DDT (219) + TX, demefione (1037) + TX, demefione-O (1037) + TX, demefione-S (1037) + TX, demeton (1038) + TX, demeton-methyl (224) + TX, demeton-O (1038) + TX, demeton-O- Methyl (224) + TX, demeton-S (1038) + TX, demeton-S-methyl (224) + TX, demeton-S-methylsulfone (1039) + TX, diafenthiuron (226) + TX, diariphos (1042) + TX, Diazinon 227) + TX, dichlorfluanide (230) + TX, dichlorvos (236) + TX, dicrifos + TX, dichophor (242) + TX, dicrotophos (243) + TX, dienochlor (1071) + TX, dimehox (1081) + TX, dimethoate (262) + TX , Ginactin (653) + TX, Gynex (1089) + TX, Gynex-dicrexin (1089) + TX, Dinobutone (269) + TX, Dinocup (270) + TX, Dinocup-4 [CCN] + TX, Dinocup-6 [CCN] + TX, Dinocton (1090) + TX, Dinopentone (1092) + TX, Dinosulfone (1097) + TX, Dinoterbon (1098) + TX, Dioxathion (1102) + TX, Diphenylsulfone (IUPAC name) (11 03) + TX, disulfiram [CCN] + TX, disulfotone (278) + TX, DNOC (282) + TX, dofenapine (1113) + TX, doramectin [CCN] + TX, endosulfan (294) + TX, endthione (1121) + TX, EPN (297) + TX, eprinomectin [CCN] + TX, ethion (309) + TX, ethoate-methyl (1134) + TX, etoxazole (320) + TX, etrimphos (1142) + TX, phenazaflor (1147) + TX, phenazaquin (328) + TX, fenbutatin oxide (330) ) + TX, phenothiocarb (337) + TX, fenpropatoline (342) + TX, fenpyrad + TX, fenpyroximate (345) + TX, Fenson (1157) TX, phentriphanyl (1161) + TX, fenvalerate (349) + TX, fipronil (354) + TX, fluacrylpyrim (360) + TX, fluazurone (1166) + TX, flubenzimine (1167) + TX, flucycloxuron (366) + TX, Flucitrinate (367) + TX, fluenethyl (1169) + TX, flufenoxuron (370) + TX, flumethrin (372) + TX, fluorbenside (1174) + TX, fulvalinate (1184) + TX, FMC 1137 (development code) (1185) + TX, formateate (405) + TX, formatenate hydrochloride (405) + TX, formotione (1192) + TX, formparanate (1193) + TX, γ-HCH (430) + TX, glio (1205) + TX, Halfenprox (424) + TX, heptenophos (432) + TX, hexadecylcyclopropanecarboxylate (IUPAC / chemical abstract name) (1216) + TX, hexythiazox (441) + TX, iodomethane (IUPAC name) ) (542) + TX, isocarbophos (473) + TX, isopropyl O- (methoxyaminothiophosphoryl) salicylate (IUPAC name) (473) + TX, ivermectin [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX , Iodofenphos (1248) + TX, lindane (430) + TX, lufenuron (490) + TX, malathion (492) + TX, malonoben (1254) + TX, mecarbam (502) + TX, mephospholane (1261) + TX, mesulfen [CCN] + TX, methaclifos (1266) + TX, methamidophos (527) + TX, methidathione (529) + TX, methiocarb (530) + TX, methomyl (531) + TX, methyl bromide (537) + TX, metorcarb (550) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime [CCN] + TX, mipahox (1293) + TX, monocrotophos (561) + TX, morphathione (1300) + TX, moxidectin [CCN] + TX, nared (567) + TX, NC-184 (compound code) + TX, NC-512 (compound code) + TX, niflurigide (1309) + TX Nicomycin [CCN] + TX, Nitrilacarb (1313) + TX, Nitrilacarb 1: 1 zinc chloride complex (1313) + TX, NNI-0101 (Compound code) + TX, NNI-0250 (Compound code) + TX, Omethoate (594) + TX, Oxamyl ( 602) + TX, oxydeprophos (1324) + TX, oxydisulfotone (1325) + TX, pp′-DDT (219) + TX, parathion (615) + TX, permethrin (626) + TX, petroleum (628) + TX, fencapton (1330) ) + TX, Fentate (631) + TX, Folate (636) + TX, Hosalon (637) + TX, Phosphorane (1338) + TX, Phosmet (638) + TX, Phosphamidone (639) + TX, Hoxim (642) TX, pyrimiphos-methyl (652) + TX, polychloroterpene (common name) (1347) + TX, polynactin (653) + TX, prochronol (1350) + TX, profenofos (662) + TX, promasil (1354) + TX, propargite ( 671) + TX, propetanephos (673) + TX, propoxer (678) + TX, protidathione (1360) + TX, protoate (1362) + TX, pyrethrin I (696) + TX, pyrethrin II (696) + TX, pyrethrin (696) + TX, pyridaben (TX) 699) + TX, pyridafenthione (701) + TX, pyrimidifen (706) + TX, pyrimidate (1370) + TX, quinalphos (711) + TX, quinthiofos (13) 1) + TX, R-1492 (development code) (1382) + TX, RA-17 (development code) (1383) + TX, rotenone (722) + TX, shuradan (1389) + TX, cebuphos + TX, ceramectin [CCN] + TX, SI -0009 (compound code) + TX, sofamid (1402) + TX, spirodiclofen (738) + TX, spiromesifen (739) + TX, SSI-121 (development code) (1404) + TX, sulfiram [CCN] + TX, sulfuramide ( 750) + TX, sulfotep (753) + TX, sulfur (754) + TX, SZI-121 (development code) (757) + TX, τ-fulvalinate (398) + TX, tebufenpyrad (763) + TX, TEPP (1417) + TX, telbum + TX, Trachlorvinphos (777) + TX, tetradiphone (786) + TX, tetranactin (653) + TX, tetrasulfur (1425) + TX, thiaphenox + TX, thiocarboxym (1431) + TX, thiophanox (800) + TX, thiomethone ( 801) + TX, thioquinox (1436) + TX, thuringiensine [CCN] + TX, triamifos (1441) + TX, trilatene (1443) + TX, triazophos (820) + TX, triazurone + TX, trichlorfone (824) + TX, trifenofos (1455) + TX An acaricide selected from the group of substances consisting of (653) + TX, bamidthione (847) + TX, vaniliprol [CCN] and YI-5302 (compound code) + TX,
Betoxazine [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, sibutrin [CCN] + TX, dicron (1052) + TX, dichlorophen (232) + TX, endtal (295) + TX , Fentin (347) + TX, slaked lime [CCN] + TX, narvum (566) + TX, quinoclamin (714) + TX, quinonamide (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) and water An algicidal agent selected from the group of substances consisting of triphenyltin oxide (IUPAC name) (347) + TX,
Abamectin (1) + TX, Kurfomato (1011) + TX, Doramectin [CCN] + TX, Emamectin (291) + TX, Emamectin benzoate (291) + TX, Eplinomectin [CCN] + TX, Ivermectin [CCN] + TX, Milbemycin oxime [CCN] An anthelmintic agent selected from the group consisting of: + TX, moxidectin [CCN] + TX, piperazine [CCN] + TX, selamectin [CCN] + TX, spinosad (737) and thiophanate (1435) + TX,
A biocide selected from the group of substances consisting of chloralose (127) + TX, endrin (1122) + TX, fenthion (346) + TX, pyridine-4-amine (IUPAC name) (23) and strychnine (745) + TX,
1-hydroxy-1H-pyridine-2-thione (IUPAC name) (1222) + TX, 4- (quinoxalin-2-ylamino) benzenesulfonamide (IUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (IUPAC name) (170) + TX, copper hydroxide (IUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1105) + TX , Dodisine (1112) + TX, phenaminosulf (1144) + TX, formaldehyde (404) + TX, hydrolgafen [CCN] + TX, kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (483) + TX, nickel bis (dimethyldithiocarbamate) (IUPAC name) (1308) + TX, nitrapirine (580) + TX, octylinone (590) + TX, oxophosphate (606) + TX, oxytetracycline (611) + TX, potassium hydroxyquinoline sulfate (446) + TX, probenazole ( 658) + TX, streptomycin (744) + TX, sesquisulfate streptomycin (744) + TX, teclophthalam (766) + TX, and a fungicide selected from the group of substances consisting of thiomersal [CCN] + TX,
Adoxyphys orana GV (12) + TX, Agrobacterium radiobacter (13) + TX, Amblyseius spp. (19) + TX, Anagrapha falphia A ) + TX, Anagrus atomus (29) + TX, Aphelinus abdominalis (33) + TX, Aphidius colimani (34) + TX, Aphidites aphidoles , Autographer Autographa californica NPV (38) + TX, Bacillus films (48) + TX, Bacillus sphaericus Neide (scientific name) (49) + TX Bacillus thuringiensis Berliner (scientific name) (51) + TX, Bacillus thuringiensis subsp. Aisawai (scientific name) (51) + TX, Bacillus thuringiensis is suiss (Scientific name) (51) TX, Bacillus thuringiensis subsp. Japonensis (scientific name) (51) + TX, Bacillus thuringiensis subspecies Kurstaki (Study), Bacillus thuringiensis subsp. Subspecies Tenebrionis (scientific name) (51) + TX, Beauveria bassiana (53) + TX, Beauveria broniali (Beauveria nerio carnea) (151) + TX, Cryptoraemus monttrozieri (178) + TX, Cydia pomonella GV (191) + TX, Hydrangea cybiiD 254) + TX, Encarsia formosa (scientific name) (293) + TX, Eretmocerus eremicus (300) + TX, Helicoverpa zea NPV (431) TPV (431) (Heterorhabditis bacteriophora) and H H. megidis (433) + TX, Hippodamia convergens (442) + TX, Leptomastix dactylopii (488) + TX, Macrolohus g (Mamestra brassicae) NPV (494) + TX, Metaphycus helvolus (522) + TX, Metalithium anisoprie var. ium anisopliae var. anisopliae) (scientific name) (523) + TX, Neodipion serpenter NPV and N. cerevisiae. Reconti (N. lecontei) NPV (575) + TX, Orius spp. (596) + TX, Paecilomyces fumosoroseus (613) + TX, Phytoseiulus p ) Multicapsid nuclear polyhedrosis virus (scientific name) (741) + TX, Steinernema bibionis (742) + TX, Steinerne carpocapsae (742) + te + TX , Steinernema glaseri (742) + TX, Steinernema riobrave (742) + TX, Steinernema riobravis (Stenernema riobine (Stenernema riobine) Steinernema spp. (742) + TX, Trichogramma spp. (826) + TX, Typhrodromus occidentalis (844) and Verticillium relicum (Verticili) Biological agent selected from the group of materials consisting of 48) + TX,
A soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537) + TX;
Aphorate [CCN] + TX, Bisadil [CCN] + TX, Busulfan [CCN] + TX, Diflubenzuron (250) + TX, Dimatif [CCN] + TX, Hemel [CCN] + TX, Hempa [CCN] + TX, Metepa [CCN] + TX, Methiotepa [CCN] + TX, methyl afolate [CCN] + TX, morzide [CCN] + TX, penflurone [CCN] + TX, tepa [CCN] + TX, thiohempa [CCN] + TX, thiotepa [CCN] + TX, tretamine [CCN] and uredepa [CC] A fertility agent selected from the group of substances consisting of CCN] + TX,
(E) -dec-5-en-1-yl acetate and (E) -dec-5-en-1-ol (IUPAC name) (222) + TX, (E) -tridec-4-en-1-yl Acetate (IUPAC name) (829) + TX, (E) -6-methylhept-2-en-4-ol (IUPAC name) (541) + TX, (E, Z) -tetradeca-4,10-diene-1- Ile acetate (IUPAC name) (779) + TX, (Z) -Dodec-7-en-1-yl acetate (IUPAC name) (285) + TX, (Z) -Hexadeca-11-enal (IUPAC name) (436) + TX, (Z) -hexadec-11-en-1-yl acetate (IUPAC name) (437) + TX, (Z) -hexadec-13-en-11-in-1-yl acetate (I (PAC name) (438) + TX, (Z) -icosa-13-en-10-one (IUPAC name) (448) + TX, (Z) -tetradec-7-en-1-al (IUPAC name) (782) + TX, (Z) -tetradec-9-en-1-ol (IUPAC name) (783) + TX, (Z) -tetradec-9-en-1-yl acetate (IUPAC name) (784) + TX, (7E, 9Z) -Dodeca-7,9-dien-1-yl acetate (IUPAC name) (283) + TX, (9Z, 11E) -Tetradeca-9,11-dien-1-yl acetate (IUPAC name) (780) + TX (9Z, 12E) -Tetradeca-9,12-dien-1-yl acetate (IUPAC name) (781) + TX, 14-methyloctadeca-1-ene (IUPA) No.) (545) + TX, 4-methylnonan-5-ol and 4-methylnonan-5-one (IUPAC name) (544) + TX, α-multistriatin [CCN] + TX, brevicomin [CCN] + TX, chodrorea [CCN ] + TX, Codremon (167) + TX, Kuhlua (179) + TX, Disparua (277) + TX, Dodec-8-en-1-yl acetate (IUPAC name) (286) + TX, Dodec-9-en-1-yl Acetate (IUPAC name) (287) + TX, dodeca-8 + TX, 10-dien-1-yl acetate (IUPAC name) (284) + TX, Dominical A [CCN] + TX, ethyl 4-methyloctanoate (IUPAC name) (317) + TX, Eugenol [CCN] + TX, Frontalin [CCN + TX, gossip lure (420) + TX, ground lure (421) + TX, ground lure I (421) + TX, ground lure II (421) + TX, ground lure III (421) + TX, ground lure IV (421) + TX, hexalua [CCN ] + TX, Ipsdienol [CCN] + TX, Ipsenol [CCN] + TX, Japonirua (481) + TX, Lineatin [CCN] + TX, Littleua [CCN] + TX, Lulua [CCN] + TX, Medorea [CCN] + TX, Megatomoic acid CCN] + TX, Methyleugenol (540) + TX, Muscarua (563) + TX, Octadeca-2,13-dien-1-yl acetate (IUPAC name) (588) + TX, Octadeca-3,13-dien-1-yl acetate (IUP C name) (589) + TX, Orfuralua [CCN] + TX, Orcturua (317) + TX, Ostramon [CCN] + TX, Sigurua [CCN] + TX, Solzidine (736) + TX, Sulcatol [CCN] + TX, Tetradec-11-ene- 1-yl acetate (IUPAC name) (785) + TX, trimedorua (839) + TX, trimedorua A (839) + TX, trimedorua B ₁ (839) + TX, trimedorua B ₂ (839) + TX, trimedorua C (839) and trunk- An insect pheromone selected from the group of substances consisting of trunc-call [CCN] + TX;
2- (octylthio) ethanol (IUPAC name) (591) + TX, butopyronoxyl (933) + TX, butoxy (polypropylene glycol) (936) + TX, dibutyl adipate (IUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX Dibutyl succinate (IUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethylcarbate [CCN] + TX, dimethyl [CCN] + TX, ethylhexanediol (1137) + TX, hexaamide [CCN] + TX An insect repellent selected from the group of substances consisting of, methkin-butyl (1276) + TX, methyl neodecanamide [CCN] + TX, oxamate [CCN] and picaridin [CCN] + TX,
1-dichloro-1-nitroethane (IUPAC / chemical abstract name) (1058) + TX, 1,1-dichloro-2,2-bis (4-ethylphenyl) ethane (IUPAC name) (1056), + TX, 1 , 2-dichloropropane (IUPAC / Chemical Abstracts name) (1062) + TX, 1,2-dichloropropane and 1,3-dichloropropene (IUPAC name) (1063) + TX, 1-bromo-2-chloroethane (IUPAC) / Chemical Abstracts Name) (916) + TX, 2,2,2-trichloro-1- (3,4-dichlorophenyl) ethyl acetate (IUPAC name) (1451) + TX, 2,2-dichlorovinyl 2-ethylsulfinyl Ethyl methyl phosphate (IUPAC name) (1066) + TX, 2- ( , 3-dithiolan-2-yl) phenyldimethylcarbamate (IUPAC / chemical abstract name) (1109) + TX, 2- (2-butoxyethoxy) ethyl thiocyanate (IUPAC / chemical abstract name) (935) + TX, 2- (4,5-dimethyl-1,3-dioxolan-2-yl) phenylmethylcarbamate (IUPAC / chemical abstract name) (1084) + TX, 2- (4-chloro-3,5-xylyloxy) ethanol (IUPAC name) (986) + TX, 2-chlorovinyldiethyl phosphate (IUPAC name) (984) + TX, 2-imidazolidone (IUPAC name) (1225) + TX, 2-isovalerylindane-1,3-dione (IUPAC) Name) (1246) + TX, 2-methyl P-2-ynyl) aminophenylmethylcarbamate (IUPAC name) (1284) + TX, 2-thiocyanatoethyl laurate (IUPAC name) (1433) + TX, 3-bromo-1-chloroprop-1-ene (IUPAC name) ) (917) + TX, 3-methyl-1-phenylpyrazol-5-yldimethylcarbamate (IUPAC name) (1283) + TX, 4-methyl (prop-2-ynyl) amino-3,5-xylylmethylcarbamate ( IUPAC name) (1285) + TX, 5,5-dimethyl-3-oxocyclohex-1-enyldimethylcarbamate (IUPAC name) (1085) + TX, abamectin (1) + TX, acephate (2) + TX, acetamiprid (4) + TX, acetylone [CCN] + TX, acetoprole [ CCN] + TX, Acrinatrin (9) + TX, Acrylonitrile (IUPAC name) (861) + TX, Aranicarb (15) + TX, Aldicarb (16) + TX, Aldoxycarb (863) + TX, Aldrin (864) + TX, Allesrin (17) + TX, allosamidine [CCN] + TX, alixicarb (866) + TX, α-cypermethrin (202) + TX, α-ecdysone [CCN] + TX, aluminum phosphide (640) + TX, amidithione (870) + TX, amidothioate (872) ) + TX, aminocarb (873) + TX, amiton (875) + TX, amiton hydrogen oxalate (875) + TX, amitraz (24) + TX, anabasine (877) + TX, atidachione (883) + TX, AVI 382 (compound) Code) + TX, AZ 60541 (compound code) + TX, azadirachtin (41) + TX, azamethiphos (42) + TX, azine phos-ethyl (44) + TX, azine phos-methyl (45) + TX, azotoate (889) + TX, Bacillus thurigen Cis (Bacillus thuringiensis) delta endotoxin (52) + TX, barium hexafluorosilicate [CCN] + TX, barium polysulfide (IUPAC / chemical abstract name) (892) + TX, bartholin [CCN] + TX, Bayer 22/190 ( Development code) (893) + TX, Bayer 22408 (development code) (894) + TX, Bengiocarb (58) + TX, Benfuracarb (60) + TX, Bensulfap (66) + TX, β- Cyfluthrin (194) + TX, β-Cypermethrin (203) + TX, Bifenthrin (76) + TX, Bioalletrin (78) + TX, Bioalletrin S-cyclopentenyl isomer (79) + TX, Bioethanomethrin [CCN] + TX, Biopermethrin (908) + TX, bioresmethrin (80) + TX, bis (2-chloroethyl) ether (IUPAC name) (909) + TX, bistrifluron (83) + TX, borax (86) + TX, brofenvalerate + TX, bromfenbin Phos (914) + TX, Bromocyclene (918) + TX, Bromo-DDT [CCN] + TX, Bromophos (920) + TX, Bromophos-ethyl (921) + TX, Bufencarb (924) + TX, Buprofezin (99) + TX, Butaka Bu (926) + TX, Butathiophos (927) + TX, Butocarboxyme (103) + TX, Butonate (932) + TX, Butoxycarboxyme (104) + TX, Butylpyridaben + TX, Kazusafos (109) + TX, Calcium Arsenate [CCN] + TX, calcium cyanide (444) + TX, calcium polysulfide (IUPAC name) (111) + TX, camphechlor (941) + TX, carbanolate (943) + TX, carbaryl (115) + TX, carbofuran (118) + TX, carbon disulfide ( IUPAC / Chemical Abstracts Name) (945) + TX, Carbon Tetrachloride (IUPAC Name) (946) + TX, Carbophenothione (947) + TX, Carbosulfan (119) + TX, Cartap (123) + TX, Cartap Hydrochloric Acid Salt (123) + TX, sebazine (725) + TX, chlorbicyclene (960) + TX, chlordan (128) + TX, chlordecone (963) + TX, chlordiform (964) + TX, chlordiform hydrochloride (964) + TX, chlorethoxyphos ( 129) + TX, chlorfenapyr (130) + TX, chlorfenvinphos (131) + TX, chlorfluazuron (132) + TX, chlormefos (136) + TX, chloroform [CCN] + TX, chloropicrin (141) + TX, chloroxime (989) ) + TX, Chlorprazophos (990) + TX, Chlorpyrifos (145) + TX, Chlorpyrifos-methyl (146) + TX, Chlorthiofos (994) + TX, Chromafenozide (150) + TX, Cineline I (6 6) + TX, Cineline II (696) + TX, Cineline (696) + TX, cis-resmethrin + TX, cismethrin (80) + TX, crocitrin + TX, cloetocarb (999) + TX, crosantell [CCN] + TX, clothianidin (165) + TX, Copper acetoarsenite [CCN] + TX, copper arsenate [CCN] + TX, copper oleate [CCN] + TX, coumaphos (174) + TX, cumitoate (1006) + TX, crotamiton [CCN] + TX, crotoxyphos (1010) + TX, Kurfomate (1011) + TX, cryolite (177) + TX, CS 708 (development code) (1012) + TX, cyanophenphos (1019) + TX, cyanophos (184) + TX, cyanate (1020) + TX, citrine [CCN] TX, cycloprotorin (188) + TX, cyfluthrin (193) + TX, cyhalothrin (196) + TX, cypermethrin (201) + TX, ciphenothrin (206) + TX, cyromazine (209) + TX, cythioate [CCN] + TX, d− Limonene [CCN] + TX, d-tetramethrin (788) + TX, DAEP (1031) + TX, dazomet (216) + TX, DDT (219) + TX, decarbofuran (1034) + TX, deltamethrin (223) + TX, demefione (1037) + TX , Demefion-O (1037) + TX, Demefion-S (1037) + TX, Demeton (1038) + TX, Demeton-methyl (224) + TX, Demeton-O (1038) + TX, Demeton-O-methyl (224) TX, demeton-S (1038) + TX, demeton-S-methyl (224) + TX, demeton-S-methylsulfone (1039) + TX, diafenthiuron (226) + TX, diariphos (1042) + TX, diamidaphos (1044) + TX, diazinon (227) + TX, dicapton (1050) + TX, diclofenthion (1051) + TX, dichlorvos (236) + TX, dicrifos + TX, dicresyl [CCN] + TX, dicrotophos (243) + TX, dicyclanyl (244) + TX, diel ) + TX, diethyl 5-methylpyrazol-3-ylphosphate (IUPAC name) (1076) + TX, diflubenzuron (250) + TX, dilol [CCN] + TX, dimeflutrin [CCN] + TX, di Mehox (1081) + TX, Dimethane (1085) + TX, Dimethoate (262) + TX, Dimethrin (1083) + TX, Dimethylvinphos (265) + TX, Dimethylan (1086) + TX, Dinex (1089) + TX, Dinex-Dicrexin (1089) + TX, dinoprop (1093) + TX, dinosum (1094) + TX, dinocebu (1095) + TX, dinotefuran (271) + TX, diophenolane (1099) + TX, dioxabenzophos (1100) + TX, dioxacarb (1101) + TX, dioxathion (1102) ) + TX, disulfotone (278) + TX, diticlophos (1108) + TX, DNOC (282) + TX, doramectin [CCN] + TX, DSP (1115) + TX, ecdysterone CCN] + TX, EI 1642 (Development Code) (1118) + TX, Emamectin (291) + TX, Emamectin Benzoate (291) + TX, EMPC (1120) + TX, Empentrin (292) + TX, Endosulfan (294) + TX, Endione ( 1121) + TX, Endrin (1122) + TX, EPBP (1123) + TX, EPN (297) + TX, Epofenonan (1124) + TX, Eprinomectin [CCN] + TX, Esfenvalerate (302) + TX, Etaphos [CCN] + TX, Ethiophene Carb ( 308) + TX, Ethion (309) + TX, Ethiprole (310) + TX, Ethoate-Methyl (1134) + TX, Etoprophos (312) + TX, Ethyl formate (IUPAC name) [CC ] + TX, ethyl-DDD (1056) + TX, ethylene dibromide (316) + TX, ethylene dichloride (chemical name) (1136) + TX, ethylene oxide [CCN] + TX, etofenprox (319) + TX, etrimphos (1142) + TX, EXD (1143) + TX, fan fur (323) + TX, phenamiphos (326) + TX, phenazaflor (1147) + TX, fenchlorphos (1148) + TX, phenetacarb (1149) + TX, fenfluthrin (1150) + TX, fenitrothion (335) + TX, Fenobucarb (336) + TX, Phenoxacrime (1153) + TX, Phenoxycarb (340) + TX, Fenpyritrin (1155) + TX, Fenpropatoline (342) + TX, Fen Rad + TX, fensulfothion (1158) + TX, fenthion (346) + TX, fenthion - ethyl [CCN] + TX, fenvalerate (349) + TX, fipronil (354) + TX, flonicamid (358) + TX, flubendiamide (CAS. Registration number: 272451-65-7) + TX, flucofuron (1168) + TX, flucycloxuron (366) + TX, flucitrinate (367) + TX, fluenethyl (1169) + TX, flufenerim [CCN] + TX, flufenoxuron ( 370) + TX, flufenprox (1171) + TX, flumethrin (372) + TX, fulvalinate (1184) + TX, FMC 1137 (development code) (1185) + TX, phonofos (1191) + TX, formethanate (405) + TX, formatenate hydrochloride (405) + TX, formothione (1192) + TX, formparanate (1193) + TX, phosmethylan (1194) + TX, hospirate (1195) + TX, phostiazate (408) + TX
, Phosthietane (1196) + TX, Furatiocarb (412) + TX, Frethrin (1200) + TX, γ-cyhalothrin (197) + TX, γ-HCH (430) + TX, Guazatine (422) + TX, Guazatine acetate (422) + TX, GY− 81 (development code) (423) + TX, halfenprox (424) + TX, halofenozide (425) + TX, HCH (430) + TX, HEOD (1070) + TX, heptachlor (1211) + TX, heptenophos (432) + TX, heterophos [ CCN] + TX, hexaflumuron (439) + TX, HHDN (864) + TX, hydramethylnon (443) + TX, hydrogen cyanide (444) + TX, hydroprene (445) + TX, hickencarb (1223) + TX, imidac Loprid (458) + TX, Imiprothrin (460) + TX, Indoxacarb (465) + TX, Iodomethane (IUPAC name) (542) + TX, IPSP (1229) + TX, Isazophos (1231) + TX, Isobenzan (1232) + TX, Isocarbophos ( 473) + TX, isodoline (1235) + TX, isofenphos (1236) + TX, isolane (1237) + TX, isoprocarb (472) + TX, isopropyl O- (methoxyaminothiophosphoryl) salicylate (IUPAC name) (473) + TX, isoprothiolane (474) ) + TX, isothioate (1244) + TX, isoxathione (480) + TX, ivermectin [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX, iodofenphos (1248) + TX, juvenile hormone I [CCN] + TX, juvenile hormone II [CCN] + TX, juvenile hormone III [CCN] + TX, kerebane (1249) + TX, quinoprene (484) + TX, λ -Cyhalothrin (198) + TX, lead arsenate [CCN] + TX, lepimectin (CCN) + TX, leptophos (1250) + TX, lindane (430) + TX, lilimfos (1251) + TX, rufenuron (490) + TX, litidathione (1253) + TX M-cumenylmethylcarbamate (IUPAC name) (1014) + TX, magnesium phosphide (IUPAC name) (640) + TX, malathion (492) + TX, malonoben (1254) + TX, majidox (1255) + TX, mecarbam (502 ) + TX, mecarphone (1258) + TX, menazone (1260) + TX, mephospholane (1261) + TX, mercuric chloride (513) + TX, mesulfenphos (1263) + TX, metaflumizone (CCN) + TX, metam (519) + TX, metam-potassium (519) + TX, metam-sodium (519) + TX, methaclifos (1266) + TX, methamidophos (527) + TX, methanesulfonyl fluoride (IUPAC / chemical abstract name) (1268) + TX, methidathion (529) + TX, methiocarb (530) + TX, Metoclotofos (1273) + TX, Metomil (531) + TX, Metoprene (532) + TX, Metokin-Butyl (1276) + TX, Metothrin (533) + TX, Methoxychlor (5 4) + TX, Methoxyphenozide (535) + TX, Methyl bromide (537) + TX, Methyl isothiocyanate (543) + TX, Methyl chloroform [CCN] + TX, Methylene chloride [CCN] + TX, Metofluthrin [CCN] + TX, Metolcarb (550) + TX, methoxadiazone (1288) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime [CCN] + TX, mipahox (1293) + TX, milex (1294) + TX, monocrotophos (561) + TX, morphothion (1300) + TX, moxidectin [CCN] + TX, naphthalophos [CCN] + TX, nared (567) + TX, naphthalene (IUPAC / chemical Structure name) (1303) + TX, NC-170 (development code) (1306) + TX, NC-184 (compound code) + TX, nicotine (578) + TX, nicotine sulfate (578) + TX, niflurigide (1309) + TX, nitenpyram ( 579) + TX, nithiazine (1311) + TX, nitriracarb (1313) + TX, nitriracarb 1: 1 zinc chloride complex (1313) + TX, NNI-0101 (compound code) + TX, NNI-0250 (compound code) + TX, nornicotine (common name) ) (1319) + TX, Novallon (585) + TX, Nobiflumuron (586) + TX, O-5-dichloro-4-iodophenyl O-ethylethylphosphonothioate (IUPAC name) (1057) + TX, O, O-diethyl O -4-methyl Ru-2-oxo-2H-chromen-7-yl phosphorothioate (IUPAC name) (1074) + TX, O, O-diethyl O-6-methyl-2-propylpyrimidin-4-yl phosphorothioate (IUPAC name) (1075) + TX, O, O, O ′, O′-tetrapropyldithiopyrophosphate (IUPAC name) (1424) + TX, oleic acid (IUPAC name) (593) + TX, ometoate (594) + TX, oxamyl (602) + TX, oxydemeton -Methyl (609) + TX, Oxydeprophos (1324) + TX, Oxydisulfotone (1325) + TX, pp'-DDT (219) + TX, Para-dichlorobenzene [CCN] + TX, Parathion (615) + TX, Parathion-methyl ( 616) + TX, penfullon [ CN] + TX, pentachlorophenol (623) + TX, pentachlorophenyl laurate (IUPAC name) (623) + TX, permethrin (626) + TX, petroleum (628) + TX, PH 60-38 (development code) (1328) + TX, Fencapton (1330) + TX, phenothrin (630) + TX, phentoate (631) + TX, folate (636) + TX, hosalon (637) + TX, phospholane (1338) + TX, phosmet (638) + TX, phosniklor (1339) + TX, Phosphamidone (639) + TX, Phosphine (IUPAC name) (640) + TX, Hoxime (642) + TX, Hoxime-methyl (1340) + TX, Pyrimetaphos (1344) + TX, Pirimicarb (651) + TX, Pirimi S-ethyl (1345) + TX, pyrimiphos-methyl (652) + TX, polychlorodicyclopentadiene isomer (IUPAC name) (1346) + TX, polychloroterpene (common name) (1347) + TX, potassium arsenite [CCN] + TX, potassium thiocyanate [CCN] + TX, praretrin (655) + TX, plecocene I [CCN] + TX, plecocene II [CCN] + TX, plecocene III [CCN] + TX, primidophos (1349) + TX, profenofos (662) + TX, profluthrin [ CCN] + TX, promasil (1354) + TX, promecarb (1355) + TX, propaphos (1356) + TX, propetanephos (673) + TX, propoxer (678) + TX, protidation (1360) + T , Prothiophos (686) + TX, protoate (1362) + TX, protrifen bute [CCN] + TX, pymetrozine (688) + TX, pyracrofos (689) + TX, pyrazophos (693) + TX, pyrethmethrin (1367) + TX, pyrethrin I (696) ) + TX, pyrethrin II (696) + TX, pyrethrin (696) + TX, pyridaben (699) + TX, pyridalyl (700) + TX, pyridafenthione (701) + TX, pyrimidifene (706) + TX, pyrimidate (1370) + TX, pyriproxyfen ( 708) + TX, quassia [CCN] + TX, quinalphos (711) + TX, quinalphos-methyl (1376) + TX, quinothion (1380) + TX, quinthiophos (1381) + TX, R -1492 (development code) (1382) + TX, rafoxanide [CCN] + TX, resmethrin (719) + TX, rotenone (722) + TX, RU 15525 (development code) (723) + TX, RU 25475 (development code) (1386) + TX , Riania (1387) + TX, ryanodine (common name) (1387) + TX, savage (725) + TX, shuradan (1389) + TX, cebuphos + TX, ceramectin [CCN] + TX, SI-0009 (compound code) + TX, SI-0205 (Compound code) + TX, SI-0404 (Compound code) + TX, SI-0405 (Compound code) + TX, Silafluophene (728) + TX, SN 72129 (Development code) (1397) + TX, Sodium arsenite [CCN] + TX Sodium cyanide (444) + TX, sodium fluoride (IUPAC / chemical abstract name) (1399) + TX, sodium hexafluorosilicate (1400) + TX, sodium pentachlorophenoxide (623) + TX, sodium selenate (IUPAC name) ) (1401) + TX, sodium thiocyanate [CCN] + TX, sofamid (1402) + TX, spinosad (737) + TX, spiromesifene (739) + TX, spirotetramat (CCN) + TX, sulcofuron (746) + TX, sulcoflon-sodium (746) + TX, sulfuramide (750) + TX, sulfotep (753) + TX, sulfuryl fluoride (756) + TX, sulproos (1408) + TX, tar oil (758) + TX, τ− Fulvalinate (398) + TX, tadimcarb (1412) + TX, TDE (1414) + TX, tebufenozide (762) + TX, tebufenpyrad (763) + TX, tebupyrimphos (764) + TX, teflubenzuron (768) + TX, tefluthrin (769) + TX (770) + TX, TEPP (1417) + TX, teraretrin (1418) + TX, terbum + TX, terbufos (773) + TX, tetrachloroethane [CCN] + TX, tetrachlorbinphos (777) + TX, tetramethrin (787) + TX, θ− Cypermethrin (204) + TX, thiacloprid (791) + TX, thiaphenox + TX, thiamethoxam (792) + TX, ticlofos (1428) + TX, thiocarboxyme (143 ) + TX, thiocyclam (798) + TX, thiocyclam oxalate (798) + TX, thiodicarb (799) + TX, thiophanox (800) + TX, thiomethone (801) + TX, thionazine (1434) + TX, thiosultap (803) ) + TX, thiosultap-sodium (803) + TX, thuringiencine [CCN] + TX, tolfenpyrad (809) + TX, tralomethrin (812) + TX, transfluthrin (813) + TX, transpermethrin (1440) + TX, triamiphos (1441) + TX, Triazamate (818) + TX, Triazophos (820) + TX, Triazurone + TX, Trichlorfone (824) + TX, Trichlormetaphos-3 [CCN] + TX, Trichloronate (14 52) + TX, trifenofos (1455) + TX, triflumuron (835) + TX, trimetacarb (840) + TX, triprene (1459) + TX, bamidthione (847) + TX, vaniliprol [CCN] + TX, veratridine (725) + TX, veratrine (725) + TX, XMC (853) + TX, xylylcarb (854) + TX, YI-5302 (compound code) + TX, ζ-cypermethrin (205) + TX, zetamethrin + TX, zinc phosphide (640) + TX, zolaprophos (1469) And ZXI 8901 (development code) (858) + TX, cyantraniliprole [736994-63-19 + TX, chlorantraniliprole [500008-45-7] + TX, sienopyra E down [560121-52-0] + TX, cyflumetofen [400882-07-7] + TX, pyrifluquinazon [337458-27-2] + TX, spinetoram [187166-40-1 + 187166-15-0] + TX, spirotetramate [
203313-25-1] + TX, sulfoxafurol [946578-00-3] + TX, flufiprol [704886-18-0] + TX, meperfluthrin [915288-13-0] + TX, tetramethylfurthrin [84937-88 −2] + TX, triflumezopyrim (disclosed in WO 2012/092115) + TX, ε-methfurthrin [240494-71-7] + TX,
Bis (tributyltin) oxide (IUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, chloecarb (999) + TX, copper acetoarsenite [CCN] + TX, copper sulfate (172) + TX, fentin (347) + TX, ferric phosphate (IUPAC name) (352) + TX, metaaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, Pentachlorophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, tadim carb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + TX, triphenmorph (1454) + TX, trimetaca Selected from the group consisting of: (840) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX, pyriprol [394730-71-3] + TX Molluscicide,
AKD-3088 (compound code) + TX, 1,2-dibromo-3-chloropropane (IUPAC / chemical abstract name) (1045) + TX, 1,2-dichloropropane (IUPAC / chemical abstract name) (1062) + TX, 1,2-dichloropropane and 1,3-dichloropropene (IUPAC name) (1063) + TX, 1,3-dichloropropene (233) + TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide (IUPAC / Chemical Abstracts Name) (1065) + TX, 3- (4-Chlorophenyl) -5-methylrhodanine (IUPAC name) (980) + TX, 5-methyl-6-thioxo-1,3,5-thiadiazinane-3 -Ilacetic acid (IUPAC name) (1286) + TX, 6-isopente Ruaminopurine (210) + TX, Abamectin (1) + TX, Acetoprole [CCN] + TX, Alanicarb (15) + TX, Aldicarb (16) + TX, Aldoxycarb (863) + TX, AZ 60541 (Compound code) + TX, Benclothiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben + TX, kazusafos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, carbosulfan (119) + TX, chloropicrin (141) + TX, Chlorpyrifos (145) + TX, Chloetocarb (999) + TX, Cytokinin (210) + TX, Dazomet (216) + TX, DBCP (1045) + TX, DCIP (218) + TX, Diamidofos (1044) + TX, Diq Fenthion (1051) + TX, Dicrifos + TX, Dimethoate (262) + TX, Doramectin [CCN] + TX, Emamectin (291) + TX, Emamectin benzoate (291) + TX, Eplinomectin [CCN] + TX, Etoprophos (312) + TX, Dual odor Ethylene (316) + TX, phenamiphos (326) + TX, fenpyrad + TX, fensulfothion (1158) + TX, phosthiazate (408) + TX, phostietane (1196) + TX, furfural [CCN] + TX, GY-81 (development code) (423) + TX, heterophos [CCN] + TX, iodomethane (IUPAC name) (542) + TX, isamidophos (1230) + TX, isazophos (1231) + TX, ivermectin [CCN] + T , Kinetin (210) + TX, mecarphone (1258) + TX, metam (519) + TX, metam-potassium (519) + TX, metam-sodium (519) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX , Milbemycin oxime [CCN] + TX, Moxidectin [CCN] + TX, Myrothecium verrucaria composition (565) + TX, NC-184 (Compound code) + TX, Oxamyl (602) + TX, Folate (636) + TX, Phosphamidone (639) + TX, Phosphocarb [CCN] + TX, Cebufos + TX, Ceramectin [CCN] + TX, Spinosad (737) + TX, Terbum + TX, Terbufos (773) + TX, Tetrachlorothio Yen (IUPAC / Chemical Abstracts) (1422) + TX, Thiaphenox + TX, Thionazine (1434) + TX, Triazophos (820) + TX, Triazolone + TX, Xylenol [CCN] + TX, YI-5302 (Compound code) and A nematicide selected from the group of substances consisting of zeatin (210) + TX, fluenesulfone [318290-98-1] + TX,
A nitrification inhibitor selected from the group of substances consisting of potassium ethyl xanthate [CCN] and nitrapiline (580) + TX;
A plant activator selected from the group of substances consisting of acibenzoral (6) + TX, acibenzoral-S-methyl (6) + TX, probenazole (658) and reynoutria sachalinensis extract (720) + TX,
2-Isovalerylindan-1,3-dione (IUPAC name) (1246) + TX, 4- (quinoxalin-2-ylamino) benzenesulfonamide (IUPAC name) (748) + TX, α-chlorohydrin [CCN] + TX, Aluminum phosphide (640) + TX, antu (880) + TX, diarsenic trioxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodifakoum (89) + TX, bromazirone (91 ) + TX, brometaline (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorofacinone (140) + TX, cholecalciferol (850) + TX, cumulolol (1004) + TX, coumafuryl (1005) + TX, Kumate Laryl (175) + TX, Crimidine (1009) + TX, Diphenacium (246) + TX, Diphethialone (249) + TX, Difacinone (273) + TX, Ergocalciferol (301) + TX, Flocumafen (357) + TX, Fluoroacetamide (379) + TX , Flupropadine (1183) + TX, flupropadine hydrochloride (1183) + TX, γ-HCH (430) + TX, HCH (430) + TX, hydrogen cyanide (444) + TX, iodomethane (IUPAC name) (542) + TX, lindane (430) + TX, magnesium phosphide (IUPAC name) (640) + TX, methyl bromide (537) + TX, norbornamide (1318) + TX, fosacetim (1336) + TX, phosphine (IUPAC name) (640 + TX, phosphorus [CCN] + TX, pindon (1341) + TX, potassium arsenite [CCN] + TX, pyrinuron (1371) + TX, silyloside (1390) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) A rodenticide selected from the group consisting of: + TX, sodium fluoroacetate (735) + TX, strychnine (745) + TX, thallium sulfate [CCN] + TX, warfarin (851) and zinc phosphide (640) + TX,
2- (2-butoxyethoxy) ethyl piperonylate (IUPAC name) (934) + TX, 5- (1,3-benzodioxol-5-yl) -3-hexylcyclohex-2-enone (IUPAC name) ) (903) + TX, farnesol and nerolidol (324) + TX, MB-599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piperotal (1343) + TX, A synergist selected from the group of substances consisting of propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesamolin (1394) and sulfoxide (1406) + TX,
Anthraquinone (32) + TX, Chloralose (127) + TX, Copper naphthenate [CCN] + TX, Copper oxychloride (171) + TX, Diazinon (227) + TX, Dicyclopentadiene (chemical name) (1069) + TX, Guazatine (422) + TX, Guazatine acetate (422) + TX, Methiocarb (530) + TX, Pyridin-4-amine (IUPAC name) (23) + TX, Tyram (804) + TX, Trimetacarb (840) + TX, Zinc naphthenate [CCN] and Diram ( 856) an animal repellent selected from the group of substances consisting of + TX,
A virucidal agent selected from the group of substances consisting of imanin [CCN] and ribavirin [CCN] + TX;
A wound protectant selected from the group consisting of mercuric oxide (512) + TX, octyrinone (590) and thiophanate-methyl (802) + TX,
And azaconazole (60207-31-0) + TX, viteltanol [70585-36-3] + TX, bromconazole [116255-48-2] + TX, cyproconazole [94361-06-5] + TX, difenoconazole [119446-68] -3] + TX, diniconazole [83657-24-3] + TX, epoxiconazole [106325-08-0] + TX, fenbuconazole [114369-43-6] + TX, fluquinconazole [136426-54-5] + TX , Flusilazole [85509-19-9] + TX, flutriazole [76667-21-0] + TX, hexaconazole [79983-71-4] + TX, imazalyl [3554-44-0] + TX, imibenconazole [86598] 92-7] + TX, ipconazole [125225-28-7] + TX, metconazole [125116-23-6] + TX, microbutanyl [88671-89-0] + TX, pefazoate [101903-30-4] + TX, penconazole [66246- 88-6] + TX, prothioconazole [1788928-70-6] + TX, pyrifenox [88283-41-4] + TX, prochloraz [67747-09-5] + TX, propiconazole [60207-90-1] + TX, cimeconazole [149508-90-7] + TX, tebuconazole [107534-96-3] + TX, tetraconazole [112281-77-3] + TX, triadimephone [43121-43-3] + TX, triadimenol [5521 -65-3] + TX, triflumizole [99387-89-0] + TX, triticonazole [131983-72-7] + TX, ansimidol [12771-68-5] + TX, fenarimol [60168-88-9. ] + TX, Nuarimol [63284-71-9] + TX, Bupirimate [41483-43-6] + TX, Dimethylylmol [5221-53-4] + TX, Ethymol [23947-60-6] + TX, Dodemorph [1593-77-7 ] + TX, fenpropidin [67306-00-7] + TX, fenpropimorph [67564-91-4] + TX, spiroxamine [118134-30-8] + TX, tridemorph [81412-43-3] + TX, cyprodinil [121552] -61-2] + TX, mepanipiri [110235-47-7] + TX, pyrimethanil [53112-28-0] + TX, fenpicuronyl [74738-17-3] + TX, fludioxonyl [133134-86-1] + TX, benalaxyl [71626-11-4] + TX, Fulleraxyl [57646-30-7] + TX, metalaxyl [57837-19-1] + TX, R-metalaxyl [70630-17-0] + TX, off-race [58810-48-3] + TX, oxadixyl [77732-09-3 ] + TX, benomyl [17804-35-2] + TX, carbendazim [10605-21-7] + TX, debacarb [62732-91-6] + TX, fuberidazole [3878-19-1] + TX, thiabendazole [148-79- 8] + TX, black Linate [84332-86-5] + TX, Diclozoline [24201-58-9] + TX, Iprodione [36734-19-7] + TX, Microzoline [54864-61-8] + TX, Procymidone [32809-16-8] + TX , Vinclozoline [50471-44-8] + TX, Boscalid [188425-85-6] + TX, Carboxin [5234-68-4] + TX, Fenfram [24691-80-3] + TX, Flutolanil [66332-96-5] + TX, mepronil [55814-41-0] + TX, oxycarboxin [5259-88-1] + TX, penthiopyrad [183675-82-3] + TX, tifluzamide [130000-40-7] + TX, guazatine [108173-90- 6] + TX Dodine [2439-10-3] [112-65-2] (free base) + TX, iminoctazine [13516-27-3] + TX, azoxystrobin [131860-33-8] + TX, dimoxystrobin [1499961 -52-4] + TX, enesterobrin {Proc. BCPC, Int. Congr. , Glasgow, 2003, 1, 93} + TX, fluoxastrobin [361377-29-9] + TX, cresoxime-methyl [143390-89-0] + TX, methinostrobin [133408-50-1] + TX, trifloxy Strobin [141517-21-7] + TX, Orizastrobin [248593-16-0] + TX, Picoxystrobin [117428-22-5] + TX, Pyraclostrobin [175013-18-0] + TX, Felvam [ 14484-64-1] + TX, Mancozeb [8018-01-7] + TX, Maneb [12427-38-2] + TX, Methylam [9006-42-2] + TX, Propineb [12071-83-9] + TX, Tiram [ 137-26-8] + TX, Zineb [1212 -67-7] + TX, diram [137-30-4] + TX, captahol [2425-06-1] + TX, captan [133-06-2] + TX, diclofluanide [1085-98-9] + TX, fluoro Imido [41205-21-4] + TX, Holpet [133-07-3] + TX, Tolylfuranide [731-27-1] + TX, Bordeaux solution [8011-63-0] + TX, Copper hydroxide [20427-59- 2] + TX, copper oxychloride [1332-40-7] + TX, copper sulfate [7758-98-7] + TX, copper oxide [1317-39-1] + TX, mancopper [53988-93-5] + TX, oxine copper [10380-28-6] + TX, dinocup [131-72-6] + TX, nitrotar-iso Lopyr [10552-74-6] + TX, edifenphos [17109-49-8] + TX, iprobenphos [26087-47-8] + TX, isoprothiolane [50512-35-1] + TX, phosdiphen [36519-00-3] + TX, pyrazophos [13457-18-6] + TX, tolcrofos-methyl [57018-04-9] + TX, acibenzoral-S-methyl [135158-54-2] + TX, anilazine [101-05-3] + TX, Benchia Valicarb [413615-35-7] + TX, Blasticidin-S [2079-00-7] + TX, Quinomethionato [2439-01-2] + TX, Chloroneb [2675-77-6] + TX, Chlorothalonyl [1897-45 −6] + TX, cyflufenamide [1 80409-60-3] + TX, simoxanyl [57966-95-7] + TX, dicron [117-80-6] + TX, diclocimet [13920-32-4] + TX, dichromedin [62885-36-5] + TX, dichlorane [ 99-30-9] + TX, dietofencarb [87130-20-9] + TX, dimethomorph [110488-70-5] + TX, SYP-LI90 (furmorph) [21867-47-9] + TX, dithianone [3347-22-6 ] + TX, ethaboxam [162650-77-3] + TX, etridiazole [2593-15-9] + TX, famoxadone [131807-57-3] + TX, fenamidone [161326-34-7] + TX, phenoxanyl [115852-48-7 ] + X, fentin [668-34-8] + TX, ferrimzone [89269-64-7] + TX, fluazinam [79622-59-6] + TX, fluopicolide [239110-15-7] + TX, fursulfamide [106917-52-6] + TX, fenhexamide [126833-3-17-8] + TX, fosetyl-aluminum [39148-24-8] + TX, hymexazole [10004-44-1] + TX, iprovaricarb [140923-17-7] + TX, IKF-916 ( Cyazofamid) [120116-88-3] + TX, kasugamycin [6980-18-3] + TX, metasulfocarb [66952-49-6] + TX, metolaphenone [220899-03-6] + TX, pencylone [66063-05 6] + TX, phthalide [27355-22-2] + TX, polyoxin [11113-80-7] + TX, probenazole [27605-76-1] + TX, propamocarb [25606-41-1] + TX, proquinazide [189278-12- 4] + TX, Pyroxylone [57369-32-1] + TX, Quinoxyphene [124495-18-7] + TX, Kintozen [82-68-8] + TX, Sulfur [7704-34-9] + TX, Thiazinyl [223580-51- 6] + TX, triazoxide [72459-58-6] + TX, tricyclazole [41814-78-2] + TX, triphorin [26644-46-2] + TX, validamycin [37248-47-8] + TX, zoxamide (RH7281) [156052 -6 8-5] + TX, Mandipropamide [374726-62-2] + TX, Isopyrazam [8816885-58-1] + TX, Sedaxane [874967-67-6] + TX, 3-Difluoromethyl-1-methyl-1H-pyrazole-4 -Carboxylic acid (9-dichloromethylene-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl) -amide (disclosed in WO 2007/048556) + TX, 3- Difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3 ′, 4 ′, 5′-trifluoro-biphenyl-2-yl) -amide (disclosed in WO 2006/087343) + TX , [(3S, 4R, 4aR, 6S, 6aS, 12R, 12aS, 12bS) -3-[(cyclopropylcarbonyl) Xyl] -1,3,4,4a, 5,6,6a, 12,12a, 12b-decahydro-6,12-dihydroxy-4,6a, 12b-trimethyl-11-oxo-9- (3-pyridinyl) -2H, 11H naphtho [2,1-b] pyrano [3,4-e] pyran-4-yl] methyl-cyclopropanecarboxylate [915972-17-7] + TX, 1,3,5-trimethyl-N -(2-Methyl-1-oxopropyl) -N- [3- (2-methylpropyl) -4- [2,2,2-trifluoro-1-methoxy-1- (trifluoromethyl) ethyl] phenyl A biologically active compound selected from the group of substances consisting of -1H-pyrazole-4-carboxamide [926914-55-8] + TX, flupiprol [704886-18-0] + X, Cyclaniliprol [1031756-98-5] + TX, Tetranyliprol [1229654-66-3] + TX, Guadipyr (described in WO2010 / 060231) + TX and Cycloxapride (Described in WO 2005/077934) + TX.

  A reference number in square brackets after the active ingredient, for example, [3878-19-1], means a chemical abstract registration number. The above mixing partners are known. The active ingredient is “The Pesticide Manual” [The Pesticide Manual-A World Compendium; D. S. Tomlin; the British Crop Protection Council, they are listed therein with the item numbers shown in parentheses above for certain compounds; for example; The compound “abamectin” is described under item number (1). When “[CCN]” is added to a specific compound in the above, the corresponding compound is included in “Compendium of Pesticide Common Names”, which is accessible on the Internet [A. Wood; Compendium of Pesticide Common Names, (Copyright) 1995-2004]; for example, the compound “acetoprole” has an Internet address: http: // www. alanwood. net / pesticides / acetoprole. It is described in html.

  Most of the above active ingredients are referred to above by the so-called “generic name”, and the related “ISO common name” or another “common name” is used in individual cases. Where the notation is not “generic name”, the notation property used instead is shown in parentheses for the particular compound; in that case, IUPAC name, IUPAC / chemical abstract name, “chemical name”, “ The “common name”, “compound name” or “development code” is used. “CAS registration number” means a chemical abstract registration number.

  The active ingredient mixture of a compound of formula I selected from Tables 1-18 and Table P and the above active ingredients is preferably a compound selected from Tables 1-18 and Table P and the above active ingredients, 100: 1 to 1: 6000, especially 50: 1 to 1:50, more particularly 20: 1 to 1:20, even more particularly 10: 1 to 1:10, very particularly 5 1 and 1: 5 ratios (2: 1 to 1: 2 ratios are particularly preferred and 4: 1 to 2: 1 ratios are also preferred), especially 1: 1, or 5: 1, or 5: 2, or 5: 3, or 5: 4, or 4: 1, or 4: 2, or 4: 3, or 3: 1, or 3: 2, or 2: 1, or 1: 5, or 2: 5, or 3: 5, or 4: 5, or 1: 4, or 2: 4, or 3: 4, and 1: 3, or 2: 3, or 1: 2, or 1: 600, or 1: 300, or 1: 150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 4:75, or 1: 6000, or 1: 3000, or 1: 1500, or 1: 350, or 2: 350, or 4: 350, or 1: 750, or 2: 750, or It is included at a ratio of 4: 750. Their mixing ratio is based on weight.

  The above mixture may be used in a method for controlling pests, the method comprising applying a composition comprising the above mixture to the pest or its environment, but a human or animal by surgery or treatment Excludes methods for the treatment of human body and diagnostic methods performed in the human or animal body.

  A mixture comprising a compound of formula I selected from Tables 1-18 and Table P and one or more active ingredients as described above can be prepared, for example, in the form of a single ready-mix, “tank mix” A single active when applied as a combined spray mixture composed of separate formulations of a single active ingredient and sequentially, ie, in succession in a rather short period of time such as hours or days Can be applied in combination of ingredients. The order in which the compounds of formula I selected from Tables 1-18 and Table P and the active ingredients described above are applied is not critical to the practice of the invention.

  The composition according to the invention comprises a stabilizer, for example a non-epoxidized or epoxidized vegetable oil (for example epoxidized coconut oil, rapeseed oil or soybean oil), an antifoaming agent, for example silicone oil, a preservative, a viscosity modifier, Binders and / or tackifiers, fertilizers or other active ingredients for obtaining a specific effect, such as fungicides, fungicides, nematicides, plant activators, molluscicides or herbicides etc. Of additional solid or liquid auxiliaries.

  The composition according to the invention can be used, for example, by crushing, sieving and / or compressing the solid active ingredient, in the absence of an auxiliary agent and, for example, in an active ingredient homogeneous with one or more auxiliary agents. It is prepared in a manner known per se by mixing and / or grinding in the presence of at least one auxiliary. These methods for the preparation of this composition and the use of Compound I for the preparation of these compositions are also the subject of the present invention.

  Application methods for this composition, i.e. spraying, atomizing, spraying, brushing on, dressing, scattering or pouring (these are generally And the use of the composition for controlling pests of the type described above is to be used in accordance with the present invention. Is another theme. Typical concentration ratios are 0.1 to 1000 ppm, preferably 0.1 to 500 ppm of active ingredient. The application rate per hectare is generally 1-2000 g of active ingredient per hectare, in particular 10-1000 g / ha, preferably 10-600 g / ha.

  A preferred method of application in the field of crop protection is application to the foliage of plants (foliar application), and the application frequency and application rate can be selected according to the risk of infestation by the corresponding pests. Alternatively, the active ingredient is introduced by irrigating the liquid composition into the plant habitat or the solid form of the active ingredient is introduced into the plant habitat, eg soil, eg in the form of granules (soil application) Thus, the plant can be reached via the root system (systemic action). In the case of paddy rice plants, such granules can be metered into paddy fields.

  The compounds according to the invention and the compositions thereof are also suitable for the protection of plant propagation material, for example seeds such as fruits, tubers or grains, or seedlings from pests of the type described above. The propagation material can be treated with this compound prior to planting, for example, the seed can be treated before sowing. Alternatively, the compound can be applied to the seeds by immersing the seeds in a liquid composition or by applying a layer of a solid composition (coating). If the propagation material is to be planted at the site of application, the composition can also be applied to the furrow, for example during drilling. These treatment methods for plant propagation material and the plant propagation material thus treated are a further subject of the present invention. Typical treatment rates depend on the plant and the pest / fungus to be controlled and are generally 1 to 200 grams per 100 kg seed, preferably 5 to 150 grams per 100 kg seed (10 to 10 per 100 kg seed). 100 grams, etc.).

  The term seed includes, but is not limited to, true seeds, seed pieces, suckers, corn grains, bulbs, fruits, tubers, grains, rhizomes, cuttings, cut shoots, and the like. It encompasses all kinds of seeds and plant pearls, and in a preferred embodiment means authentic seeds.

  The present invention also includes seeds that are coated with or treated with a compound of formula I. The term “coated or treated with and / or containing” generally means that the active ingredient is, in most cases, on the surface of the seed at the time of application, but depending on the method of application, some of the ingredients However, it shows that it can penetrate into the seed material to some extent. When the seed product is (re) planted, it can absorb the active ingredient. In one embodiment, the present invention makes available a plant propagation material to which a compound of formula (I) is attached. In addition, this makes available compositions comprising plant propagation material treated with a compound of formula (I).

  Seed treatment includes all suitable seed treatment techniques known in the art, such as seed dressing, seed coating, seed dispersal, seed soaking and seed pelleting. Seed treatment application of the compound of formula (I) may be performed by any known method, such as by spraying or spraying seeds before sowing or during sowing / seed planting.

Biological examples:
Example B1: Activity Against Egyptian Littoralis (Egyptian Yeast) Cotton leaf pieces were placed on agar in a 24-well microtiter plate and sprayed with an aqueous test solution prepared from a 10'000 ppm DMSO stock solution. After drying, the leaf pieces were infested with 5 L1 larvae. Samples were evaluated for mortality, feeding inhibition effects, and growth inhibition compared to untreated samples 3 days after infestation. Control of Egyptian littoralis with test samples is when at least one of mortality, feeding inhibition effects and growth inhibition is higher than untreated samples. The following compounds: P1, P4, P5, P8, P9, P10, P12 and P13 are at least 80% control of at least one of three categories (mortality, feeding inhibition or growth inhibition) at an application rate of 200 ppm. Showed the effect.

Example B2: Activity Against Egyptian Littoralis (Egyptian Yeast) Test compounds from a 10'000 ppm DMSO stock solution were pipetted into 24-well plates and mixed with agar. Lettuce seeds were placed on agar and the multiwell plate was closed with another plate containing agar as well. After 7 days, the roots had absorbed the compound and lettuce had grown into the lid plate. Next, lettuce leaves were cut and placed in a lid plate. Spodoptera eggs were pipetted onto a wet gel blotting paper through a plastic stencil and the plate was closed with this blotting paper. Samples were evaluated for mortality, feeding inhibition effects and growth inhibition compared to untreated samples 6 days after infestation. The following compounds: P1, P4, P9, P12 and P13 showed at least 80% control effect of at least one of the three categories (mortality, feeding inhibition or growth inhibition) at an application rate of 12.5 ppm. .

Example B3: Activity on Plutella xylostella (Ponella) A 24-well microtiter plate with artificial feed was treated with a test aqueous solution prepared from a 10'000 ppm DMSO stock solution by pipette. After drying, the plates were infested with L2 larvae (10-15 per well). Samples were evaluated for mortality and growth inhibition compared to untreated samples 5 days after infestation. The following compounds: P1, P4, P5, P6, P8, P9, P10, P11, P12 and P13 have at least 80% effect of at least one of the two categories (mortality or growth inhibition) at a dose of 200 ppm. Indicated.

Example B4: Activity against Diabrotica balteata (Corn beetle) Corn buds placed on agar layers in 24-well microtiter plates were prepared by spraying from a 10'000 ppm DMSO stock solution. Treated with aqueous test solution. After drying, the plates were infested with L2 larvae (6-10 per well). Samples were evaluated for mortality and growth inhibition compared to untreated samples 4 days after infestation. The following compounds: P1, P4, P5, P6, P8, P9, P10, P11, P12 and P13 have at least 80% effect of at least one of the two categories (mortality or growth inhibition) at a dose of 200 ppm. Indicated.

Example B5: Activity against peach persicae (peach aphid) Sunflower leaf pieces were placed on agar in a 24-well microtiter plate and sprayed with an aqueous test solution prepared from a 10'000 ppm DMSO stock solution. After drying, the leaf pieces were infested with a population of aphids of various ages. Samples were evaluated for mortality 6 days after infestation. The following compounds: P1, P4, P5, P6, P8, P9, P10, P11, P12 and P13 resulted in at least 80% mortality at 200 ppm application rate.

Example B6: Activity against peach persicae (peach aphid) Test compounds from 10'000 ppm DMSO stock solution were pipetted into 24-well microtiter plates and mixed with sucrose solution. The plate was closed with stretched parafilm. A plastic stencil with 24 holes was placed on the plate, and the infested pea seedlings were placed directly on the parafilm. The infested plate was closed with gel blotting paper and another plastic stencil and then turned upside down. Samples were evaluated for mortality 5 days after infestation. The following compound: P1 resulted in a mortality of at least 80% at a test dose of 12 ppm.

Example B7: Activity against Tobacco whiteflies (cotton whiteflies) Cotton leaf pieces were placed on agar in a 24-well microtiter plate and sprayed with a test aqueous solution prepared from a 10'000 ppm DMSO stock solution. After drying, this leaf piece was infested with adult whiteflies. Samples were examined for mortality after 6 days of incubation. The following compounds: P4, P6, P8, P9, P10, P11, P12 and P13 resulted in at least 80% mortality at 200 ppm application rate.

Example B8: Activity against Euschistus heros (Neotropical Brown Stink Bug) Prepared from 10'000 ppm DMSO stock solution on soybean leaves on agar in 24-well microtiter plates The test aqueous solution was sprayed. After drying, the leaves were infested with N-2 nymphs. Samples were evaluated for mortality 5 days after infestation. The following compounds: P1, P4, P5, P6, P8, P9, P10, P11, P12 and P13 resulted in at least 80% mortality at 200 ppm application rate.

Example B9: Activity against peach persicae (peach aphid) Roots of pea seedlings infested with aphid populations of various ages were tested in aqueous test solutions prepared from 10'000 DMSO stock solution Put directly into. Samples were evaluated for mortality 6 days after seedlings were placed in the test solution. The following compounds: P9 and P11 resulted in at least 80% mortality at the 24 ppm test amount.

Example B10: Activity against Franklinella occidentalis (Rhizoris thrips) Sunflower leaf pieces were placed on agar in a 24-well microtiter plate and sprayed with an aqueous test solution prepared from a 10'000 DMSO stock solution. After drying, the leaf pieces were infested with different age groups of Frankliniella. Samples were evaluated for mortality 7 days after infestation. The following compounds: P4, P9, P11 and P13 resulted in a mortality of at least 80% at an application rate of 200 ppm.

Example B11: Activity Against Trips tabaci (Nember Thrips) Sunflower leaf pieces were placed on agar in a 24-well microtiter plate and sprayed with an aqueous test solution prepared from a 10'000 ppm DMSO stock solution. After drying, the leaf pieces were infested with thrips populations of various ages. Samples were evaluated for mortality 6 days after infestation. The following compounds: P9 and P13 resulted in a mortality rate of at least 80% at an application rate of 200 ppm.

Example B12: Activity against Aedes aegypti (yellow fever mosquito) The test solution was placed in a 12-well tissue culture plate at a dose of 200 ppm in ethanol. After the sediment was dried, five 2-5 day old female adult Aedes aegypti were added to each well and grown in a 10% sucrose solution in cotton wool mass. Knockdown assessments were made 1 hour after introduction and mortality was assessed 24 and 48 hours after introduction. The following compounds: P9 and P13 showed at least 80% control of Aedes aegypti after 48 hours and / or 24 hours.

Example B13: Activity against Anopheles stephensi (Indian malaria mosquito) The test solution was placed in a 12-well tissue culture plate at a dose of 200 ppm in ethanol. After the sediment was dried, five 2-5 day old female adult Anopheles stephensi were added to each well and grown in a 10% sucrose solution in cotton wool mass. Knockdown assessments were made 1 hour after introduction and mortality was assessed 24 and 48 hours after introduction. The following compounds: P4, P9 and P13 showed at least 80% control of Anopheles stephensi after 48 and / or 24 hours.

Claims (14)

Formula I

(Where
A represents CH or N;
Q is 3-position or coupled to the 4-position; and either a C ₃ -C ₆ cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ cycloalkyl , —C (O) OH, —C (O) NH ₂ , C ₃ -C ₆ cycloalkyl mono- or polysubstituted with a substituent selected from the group consisting of phenyl, and halogen, cyano, C _1- C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkylsulfinyl, C ₁ -C ₄ haloalkylsulfonyl and -C (O) C ₁ ~C be mono- or polysubstituted may phenyl with substituents selected from the _fourth group consisting of haloalkyl;
X is S, SO or SO ₂ ;
R ₁ is C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ cycloalkyl-C ₁ -C ₄ alkyl, or halogen, cyano and C ₁ -C Is C ₃ -C ₆ cycloalkyl mono- or poly-substituted with a substituent selected from the group consisting of ₄ alkyl; or R ₁ is selected from the group consisting of halogen, cyano and C ₁ -C ₄ alkyl Or C ₃ -C ₆ cycloalkyl-C ₁ -C ₄ alkyl mono- or poly-substituted with a substituent selected from R; or R ₁ is C ₂ -C ₆ alkenyl, C ₂ -C ₆ haloalkenyl or C ₂ -C ₆ alkynyl;
R ₂ is halogen, cyano, C ₁ -C ₆ haloalkyl or hydroxyl, or a C ₁ -C ₆ haloalkyl substituted with 1 or 2 substituents selected from the group consisting of methoxy and cyano; or R ₂ is C ₁ -C ₄ haloalkylsulfanyl, C ₁ -C ₄ haloalkylsulfinyl, C ₁ -C ₄ haloalkylsulfonyl, O (C ₁ -C ₄ haloalkyl), or —C (O) C ₁ -C ₄ haloalkyl. Or R ₂ is C ₃ -C ₆ cycloalkyl, which can be mono- or polysubstituted with a substituent selected from the group consisting of halogen, cyano and C ₁ -C ₄ alkyl;
X ₁ is O, S or NR ₃ , wherein R ₃ is hydrogen, C ₁ -C ₄ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₄ alkoxy- C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl)
And the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of said compounds of formula I. Formula I-1

In which R ₂ and Q are as defined in formula I according to claim 1;
Xa ₁ is S, SO or SO ₂ ; and Ra ₁ is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl)
The compound of formula I according to claim 1, which is represented by the compound of Formula I-2

In which R ₂ and Q are as defined in formula I according to claim 1;
Xa ₁ is S, SO or SO ₂ ; and Ra ₁ is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl)
The compound of formula I according to claim 1, which is represented by the compound of Formula I-3

In which R ₂ and Q are as defined in formula I according to claim 1;
Xa ₁ is S, SO or SO ₂ ; and Ra ₁ is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl)
The compound of formula I according to claim 1, which is represented by the compound of Formula Ia-1

(Where
A is CH or N;
X ₂ is S or SO ₂ ;
X ₃ is N- (C ₁ -C ₄ alkyl);
R ₄ is C ₁ -C ₄ alkyl;
R ₅ is C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkylsulfanyl; and Q _a is C ₃ -C ₆ cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₃ -C ₆ cycloalkyl mono- or polysubstituted with a substituent selected from the group consisting of —C (O) OH and —C (O) NH ₂ )
The compound of formula I according to claim 1, which is represented by the compound of Formula Ia-2

(Where
A is CH or N;
X ₄ is N- (C ₁ -C ₄ alkyl);
R ₆ is C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkylsulfanyl; and Q _b is C ₃ -C ₆ cycloalkyl, or cyano, —C (O) OH and —C (O) NH A C ₃ -C ₆ cycloalkyl monosubstituted with a substituent selected from the group consisting of ₂ )
The compound of formula I according to claim 1, which is represented by the compound of Formula Ia-3

(Where
A is CH or N;
X _2p is S or SO ₂ ;
X _3p is N- (C ₁ -C ₄ alkyl);
R _4p is C ₁ -C ₄ alkyl;
R _5p is C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkylsulfanyl; and Q _ap is C ₃ -C ₆ cycloalkyl, or halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, -C (O) OH, -C (O) with a substituent selected from the group consisting of NH ₂ and phenyl which is monosubstituted or polysubstituted C ₃ -C ₆ cycloalkyl)
The compound of formula I according to claim 1, which is represented by the compound of Formula Ia-4

(Where
A is CH or N;
X _4p is N- (C ₁ -C ₄ alkyl);
R _6p is C ₁ -C ₄ haloalkyl or C ₁ -C ₄ haloalkylsulfanyl; and Q _bp is C ₃ -C ₆ cycloalkyl, or cyano, —C (O) OH and —C (O) NH A C ₃ -C ₆ cycloalkyl monosubstituted with a substituent selected from the group consisting of ₂ )
The compound of formula I according to claim 1, which is represented by the compound of Formula VI-a

(Where
A, Q, X ₁ and R ₂ are as defined in formula I of claim 1; and Xb ₃₀ is halogen)
Compound. Formula XV-int

(Where
R ₁ , R ₂ , R ₃ , X and A are as defined in Formula I of claim 1; and Q is a group

Where R ₀₀₀₂ is cyano)
Compound.   As active ingredient at least one compound of formula I according to claim 1, or optionally a tautomer thereof, in free form or in an agrochemically usable salt form, respectively, and at least one auxiliary agent; A pesticide composition comprising:   A method for controlling a pest comprising the step of applying the composition of claim 11 to the pest or its environment, wherein the method is for the treatment of the human or animal body by surgery or treatment. And methods excluding diagnostic methods performed in the human or animal body.   A method for protecting plant propagation material from attack by pests, comprising the step of treating the propagation material or a place where the propagation material is planted with the composition of claim 11.   A plant propagation material treated according to the method of claim 13.